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Cardiomyopathy(CMYO)

MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
Synonym: CMYO
SNOMED CT: Disorder of myocardium (57809008); Disorder of heart muscle (57809008); Cardiomyopathy (85898001); Myocardiopathy (85898001); Myocardial disease (57809008)
 
Related genes: RBM20, NEXN, MYLK2, TMEM43, JPH2, MYOZ2, PRKAG2, ANKRD1, LDB3, ABCC9, BAG3, TCAP, CSRP3, VCL, TTN, TPM1, TNNT2, TNNI3, TNNC1, TMPO, TGFB3, TAFAZZIN, SGCD, SDHA, SCN5A, RYR2, PSEN2, PSEN1, PLN, PKP2, MYL3, MYL2, MYH7, MYH6, MYBPC3, LMNA, LAMA4, JUP, FKTN, EYA4, DSP, DSG2, DSC2, DES, CRYAB, CAV3, ACTN2, ACTC1
 
HPO: HP:0001638
Orphanet: ORPHA167848

Definition

A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Cardiomyopathy in Orphanet.

Conditions with this feature

Beckwith-Wiedemann syndrome
MedGen UID:
2562
Concept ID:
C0004903
Disease or Syndrome
Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.
Duchenne muscular dystrophy
MedGen UID:
3925
Concept ID:
C0013264
Disease or Syndrome
The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated dilated cardiomyopathy (DCM) when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM.
Endocardial fibroelastosis
MedGen UID:
4041
Concept ID:
C0014117
Disease or Syndrome
Endomyocardial fibroelastosis is a cause of unexplained childhood cardiac insufficiency. It results from diffuse thickening of the endocardium leading to dilated myocardiopathy in the majority of cases and restrictive myocardiopathy in rare cases. It may occur as a primary disorder or may be secondary to another cardiac malformation, notably aortic stenosis or atresia.
Glycogen storage disease type III
MedGen UID:
6641
Concept ID:
C0017922
Disease or Syndrome
Glycogen storage disease type III (GSD III) is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa is the most common subtype, present in about 85% of affected individuals; it manifests with liver and muscle involvement. GSD IIIb, with liver involvement only, comprises about 15% of all GSD III. In infancy and early childhood, liver involvement presents as ketotic hypoglycemia, hepatomegaly, hyperlipidemia, and elevated hepatic transaminases. In adolescence and adulthood, liver disease becomes less prominent. Hypertrophic cardiomyopathy develops in the majority of those with GSD IIIa, usually during childhood. Its clinical significance ranges from asymptomatic in the majority to severe cardiac dysfunction, congestive heart failure, and (rarely) sudden death. Skeletal myopathy manifesting as weakness is not usually evident in childhood, but slowly progresses, typically becoming prominent in the third to fourth decade.
Glycogen storage disease, type IV
MedGen UID:
6642
Concept ID:
C0017923
Disease or Syndrome
The clinical manifestations of glycogen storage disease type IV (GSD IV) discussed in this entry span a continuum of different subtypes with variable ages of onset, severity, and clinical features. Clinical findings vary extensively both within and between families. The fatal perinatal neuromuscular subtype presents in utero with fetal akinesia deformation sequence, including decreased fetal movements, polyhydramnios, and fetal hydrops. Death usually occurs in the neonatal period. The congenital neuromuscular subtype presents in the newborn period with profound hypotonia, respiratory distress, and dilated cardiomyopathy. Death usually occurs in early infancy. Infants with the classic (progressive) hepatic subtype may appear normal at birth, but rapidly develop failure to thrive; hepatomegaly, liver dysfunction, and progressive liver cirrhosis; hypotonia; and cardiomyopathy. Without liver transplantation, death from liver failure usually occurs by age five years. Children with the non-progressive hepatic subtype tend to present with hepatomegaly, liver dysfunction, myopathy, and hypotonia; however, they are likely to survive without progression of the liver disease and may not show cardiac, skeletal muscle, or neurologic involvement. The childhood neuromuscular subtype is rare and the course is variable, ranging from onset in the second decade with a mild disease course to a more severe, progressive course resulting in death in the third decade.
Kearns Sayre syndrome
MedGen UID:
9618
Concept ID:
C0022541
Disease or Syndrome
Mitochondrial DNA (mtDNA) deletion syndromes predominantly comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may be observed in different members of the same family or may evolve from one clinical syndrome to another in a given individual over time. The three classic phenotypes caused by mtDNA deletions are Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external ophthalmoplegia (PEO). KSS is a progressive multisystem disorder defined by onset before age 20 years, pigmentary retinopathy, and PEO; additional features include cerebellar ataxia, impaired intellect (intellectual disability, dementia, or both), sensorineural hearing loss, ptosis, oropharyngeal and esophageal dysfunction, exercise intolerance, muscle weakness, cardiac conduction block, and endocrinopathy. Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and may be fatal in infancy without appropriate hematologic management. PEO is characterized by ptosis, impaired eye movements due to paralysis of the extraocular muscles (ophthalmoplegia), oropharyngeal weakness, and variably severe proximal limb weakness with exercise intolerance. Rarely, a mtDNA deletion can manifest as Leigh syndrome.
Mucopolysaccharidosis type 6
MedGen UID:
44514
Concept ID:
C0026709
Disease or Syndrome
Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).
Phytanic acid storage disease
MedGen UID:
11161
Concept ID:
C0034960
Disease or Syndrome
Refsum disease is characterized by anosmia and early-onset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to older than age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life.
Wolff-Parkinson-White pattern
MedGen UID:
12162
Concept ID:
C0043202
Disease or Syndrome
Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).\n\nThe heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.\n\nPeople with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.\n\nComplications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.\n\nWolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body).
Mucopolysaccharidosis type 7
MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap. Affected individuals are best described as having either a phenotype consistent with either severe (Hurler syndrome) or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal, as is progressive arthropathy involving most joints. By age three years, linear growth decreases. Intellectual disability is progressive and profound but may not be readily apparent in the first year of life. Progressive cardiorespiratory involvement, hearing loss, and corneal clouding are common. Without treatment, death (typically from cardiorespiratory failure) usually occurs within the first ten years of life. Attenuated MPS I. Clinical onset is usually between ages three and ten years. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decade, to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities and psychiatric manifestations can be present later in life. Hearing loss, cardiac valvular disease, respiratory involvement, and corneal clouding are common.
Congenital heart block
MedGen UID:
57432
Concept ID:
C0149530
Disease or Syndrome
Congenital heart block (CHB) is a rare disorder of atrioventricular conduction, characterized by absence of conduction of atrial impulses to the ventricles with slower ventricular rhythm (atrioventricular dissociation). CHB can occur in association with immunological evidence of maternal connective disease (autoimmune CHD), fetal structural CHD or can be idiopathic.
Cyclical vomiting syndrome
MedGen UID:
57509
Concept ID:
C0152164
Disease or Syndrome
A condition characterized by recurrent, self-limiting episodes of vomiting associated with intense nausea, pallor, and lethargy. It is commonly a migraine precursor.
Propionic acidemia
MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by a healthy newborn with poor feeding and decreased arousal in the first few days of life, followed by progressive encephalopathy of unexplained origin. Without prompt diagnosis and management, this is followed by progressive encephalopathy manifesting as lethargy, seizures, or coma that can result in death. It is frequently accompanied by metabolic acidosis with anion gap, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Individuals with late-onset PA may remain asymptomatic and suffer a metabolic crisis under catabolic stress (e.g., illness, surgery, fasting) or may experience a more insidious onset with the development of multiorgan complications including vomiting, protein intolerance, failure to thrive, hypotonia, developmental delays or regression, movement disorders, or cardiomyopathy. Isolated cardiomyopathy can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure.
Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness
MedGen UID:
83338
Concept ID:
C0342287
Congenital Abnormality
Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia occurs between infancy and adolescence. The anemia is corrected with thiamine treatment, but the red cells remain macrocytic, and anemia can recur when treatment is withdrawn. Progressive sensorineural hearing loss has generally been early and can be detected in toddlers; hearing loss is irreversible and may not be prevented by thiamine treatment. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence. Thiamine treatment may delay onset of diabetes in some individuals.
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Disease or Syndrome
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
Deficiency of butyryl-CoA dehydrogenase
MedGen UID:
90998
Concept ID:
C0342783
Disease or Syndrome
Most infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) identified through newborn screening programs have remained well, and asymptomatic relatives who meet diagnostic criteria are reported. Thus, SCADD is now viewed as a biochemical phenotype rather than a disease. A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures, hypotonia, dystonia, and myopathy. However, individuals with no symptoms were also reported. In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. In contrast, the majority of infants with SCADD have been detected by expanded newborn screening, and the great majority of these infants remain asymptomatic. As with other fatty acid oxidation deficiencies, characteristic biochemical findings of SCADD may be absent except during times of physiologic stress such as fasting and illness. A diagnosis of SCADD based on clinical findings should not preclude additional testing to look for other causes.
Carnitine acylcarnitine translocase deficiency
MedGen UID:
91000
Concept ID:
C0342791
Disease or Syndrome
Carnitine-acylcarnitine translocase deficiency is a rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy and arrhythmias, skeletal muscle damage, and liver dysfunction. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. However, presentations at a later age with a milder phenotype have been reported (summary by Rubio-Gozalbo et al., 2004).
Congenital disorder of glycosylation, type Ia
MedGen UID:
138111
Concept ID:
C0349653
Disease or Syndrome
PMM2-CDG, the most common of a group of disorders of abnormal glycosylation of N-linked oligosaccharides, is divided into three clinical stages: infantile multisystem, late-infantile and childhood ataxia–intellectual disability, and adult stable disability. The clinical manifestations and course are highly variable, ranging from infants who die in the first year of life to mildly affected adults. Clinical findings tend to be similar in sibs. In the infantile multisystem presentation, infants show axial hypotonia, hyporeflexia, esotropia, and developmental delay. Feeding problems, vomiting, faltering growth, and developmental delay are frequently seen. Subcutaneous fat may be excessive over the buttocks and suprapubic region. Two distinct clinical courses are observed: (1) a nonfatal neurologic course with faltering growth, strabismus, developmental delay, cerebellar hypoplasia, and hepatopathy in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade; and (2) a more severe neurologic-multivisceral course with approximately 20% mortality in the first year of life. The late-infantile and childhood ataxia–intellectual disability stage, which begins between ages three and ten years, is characterized by hypotonia, ataxia, severely delayed language and motor development, inability to walk, and IQ of 40 to 70; other findings include seizures, stroke-like episodes or transient unilateral loss of function, coagulopathy, retinitis pigmentosa, joint contractures, and skeletal deformities. In the adult stable disability stage, intellectual ability is stable; peripheral neuropathy is variable, progressive retinitis pigmentosa and myopia are seen, thoracic and spinal deformities with osteoporosis worsen, and premature aging is observed; females may lack secondary sexual development and males may exhibit decreased testicular volume. Hypogonadotropic hypogonadism and coagulopathy may occur. The risk for deep venous thrombosis is increased.
McLeod neuroacanthocytosis syndrome
MedGen UID:
140765
Concept ID:
C0398568
Disease or Syndrome
McLeod neuroacanthocytosis syndrome (designated as MLS throughout this review) is a multisystem disorder with central nervous system (CNS), neuromuscular, cardiovascular, and hematologic manifestations in males: CNS manifestations are a neurodegenerative basal ganglia disease including movement disorders, cognitive alterations, and psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and muscle weakness or atrophy of different degrees. Cardiac manifestations include dilated cardiomyopathy, atrial fibrillation, and tachyarrhythmia. Hematologically, MLS is defined as a specific blood group phenotype (named after the first proband, Hugh McLeod) that results from absent expression of the Kx erythrocyte antigen and weakened expression of Kell blood group antigens. The hematologic manifestations are red blood cell acanthocytosis and compensated hemolysis. Alloantibodies in the Kell and Kx blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in affected male newborns of Kell-negative mothers. Females heterozygous for XK pathogenic variants have mosaicism for the Kell and Kx blood group antigens. Although they usually lack CNS and neuromuscular manifestations, some heterozygous females may develop clinical manifestations including chorea or late-onset cognitive decline.
Familial cutaneous collagenoma
MedGen UID:
96073
Concept ID:
C0406817
Neoplastic Process
Cataract-intellectual disability-hypogonadism syndrome
MedGen UID:
208658
Concept ID:
C0796037
Disease or Syndrome
RAB18 deficiency is the molecular deficit underlying both Warburg micro syndrome (characterized by eye, nervous system, and endocrine abnormalities) and Martsolf syndrome (characterized by similar – but milder – findings). To date Warburg micro syndrome comprises >96% of reported individuals with genetically defined RAB18 deficiency. The hallmark ophthalmologic findings are bilateral congenital cataracts, usually accompanied by microphthalmia, microcornea (diameter <10), and small atonic pupils. Poor vision despite early cataract surgery likely results from progressive optic atrophy and cortical visual impairment. Individuals with Warburg micro syndrome have severe to profound intellectual disability (ID); those with Martsolf syndrome have mild to moderate ID. Some individuals with RAB18 deficiency also have epilepsy. In Warburg micro syndrome, a progressive ascending spastic paraplegia typically begins with spastic diplegia and contractures during the first year, followed by upper-limb involvement leading to spastic quadriplegia after about age five years, often eventually causing breathing difficulties. In Martsolf syndrome infantile hypotonia is followed primarily by slowly progressive lower-limb spasticity. Hypogonadism – when present – manifests in both syndromes, in males as micropenis and/or cryptorchidism and in females as hypoplastic labia minora, clitoral hypoplasia, and small introitus.
Aicardi Goutieres syndrome 1
MedGen UID:
162912
Concept ID:
C0796126
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
Simpson-Golabi-Behmel syndrome type 1
MedGen UID:
162917
Concept ID:
C0796154
Disease or Syndrome
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is characterized by pre- and postnatal macrosomia; distinctive craniofacial features (including macrocephaly, coarse facial features, macrostomia, macroglossia, and palatal abnormalities); and commonly, mild to severe intellectual disability with or without structural brain anomalies. Other variable findings include supernumerary nipples, diastasis recti / umbilical hernia, congenital heart defects, diaphragmatic hernia, genitourinary defects, and gastrointestinal anomalies. Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. Affected individuals are at increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma, and medulloblastoma.
Toriello-Carey syndrome
MedGen UID:
163225
Concept ID:
C0796184
Disease or Syndrome
Toriello-Carey syndrome is a multiple congenital anomaly disorder with variable systemic manifestations, most commonly including mental retardation, agenesis of the corpus callosum, postnatal growth delay, cardiac defects, usually septal defects, distal limb defects, and urogenital anomalies in affected males. Patients have facial dysmorphic features, micrognathia, including full cheeks, hypertelorism, flattened nasal bridge, anteverted nares, and short neck. Not all features are found in all patients and some patients may have additional features such as anal anomalies or hernias (summary by Toriello et al., 2003). In a review of the Toriello-Carey syndrome, Toriello et al. (2016) stated that while corpus callosum abnormalities and micrognathia with highly arched or cleft palate are seen in most patients, other manifestations are widely variable. They noted that etiologic heterogeneity has been observed in reported patients, with at least 20% of patients having chromosome anomalies, and that no good candidate genes have been identified by exome sequencing. The authors commented that this condition might not be a unitary diagnostic entity. They recommended chromosome microarray for any child suspected of having the condition, followed by standard of care by genetic testing.
Becker muscular dystrophy
MedGen UID:
182959
Concept ID:
C0917713
Disease or Syndrome
The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated dilated cardiomyopathy (DCM) when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM.
Muscular dystrophy, cardiac type
MedGen UID:
254845
Concept ID:
C1442927
Disease or Syndrome
Meretoja syndrome
MedGen UID:
301243
Concept ID:
C1622345
Disease or Syndrome
The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported (Meretoja, 1973).
Congenital generalized lipodystrophy type 1
MedGen UID:
318592
Concept ID:
C1720862
Disease or Syndrome
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Limb-girdle muscular dystrophy-dystroglycanopathy, type C1
MedGen UID:
332193
Concept ID:
C1836373
Disease or Syndrome
Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (CRPPA; 614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951).
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3
MedGen UID:
373087
Concept ID:
C1836439
Disease or Syndrome
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Patients with C10ORF2-linked adPEO may have other clinical features including proximal muscle weakness, ataxia, peripheral neuropathy, cardiomyopathy, cataracts, depression, and endocrine abnormalities (summary by Fratter et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). PEO caused by mutations in the POLG gene (174763) are associated with more complicated phenotypes than those forms caused by mutations in the SLC25A4 (103220) or C10ORF2 genes (Lamantea et al., 2002).
Uruguay faciocardiomusculoskeletal syndrome
MedGen UID:
335320
Concept ID:
C1846010
Disease or Syndrome
Uruguay faciocardiomusculoskeletal syndrome (FCMSU) is an X-linked disorder in which affected males have a distinctive facial appearance, muscular hypertrophy, and cardiac ventricular hypertrophy leading to premature death. Additional features include large, broad, and deformed hands and feet, congenital hip dislocation, and scoliosis (summary by Xue et al., 2016).
Cardioneuromyopathy with hyaline masses and nemaline rods
MedGen UID:
339747
Concept ID:
C1847387
Disease or Syndrome
Glycogen storage disease of heart, lethal congenital
MedGen UID:
337919
Concept ID:
C1849813
Disease or Syndrome
Any glycogen storage disease in which the cause of the disease is a mutation in the PRKAG2 gene.
Neutral lipid storage myopathy
MedGen UID:
339913
Concept ID:
C1853136
Disease or Syndrome
Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007).
Hemochromatosis type 4
MedGen UID:
340044
Concept ID:
C1853733
Disease or Syndrome
Hemochromatosis type 4 (HFE4) is a dominantly inherited iron overload disorder with heterogeneous phenotypic manifestations that can be classified into 2 groups. One group is characterized by an early rise in ferritin (see 134790) levels with low to normal transferrin (190000) saturation and iron accumulation predominantly in macrophages. The other group is similar to classical hemochromatosis, with high transferrin saturation and prominent parenchymal iron loading (summary by De Domenico et al., 2005). For general background information and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200.
Noonan syndrome 2
MedGen UID:
344290
Concept ID:
C1854469
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
MedGen UID:
344424
Concept ID:
C1855114
Disease or Syndrome
Isolated methylmalonic acidemia/aciduria, the topic of this GeneReview, is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of the manifestations of isolated methylmalonic acidemia/aciduria ranges from the neonatal period to adulthood. All phenotypes are characterized by periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress. In the neonatal period the disease can present with lethargy, vomiting, hypotonia, hypothermia, respiratory distress, severe ketoacidosis, hyperammonemia, neutropenia, and thrombocytopenia and can result in death within the first four weeks of life. In the infantile/non-B12-responsive phenotype, infants are normal at birth, but develop lethargy, vomiting, dehydration, failure to thrive, hepatomegaly, hypotonia, and encephalopathy within a few weeks to months of age. An intermediate B12-responsive phenotype can occasionally be observed in neonates, but is usually observed in the first months or years of life; affected children exhibit anorexia, failure to thrive, hypotonia, and developmental delay, and sometimes have protein aversion and/or vomiting and lethargy after protein intake. Atypical and "benign"/adult methylmalonic acidemia phenotypes are associated with increased, albeit mild, urinary excretion of methylmalonate. Major secondary complications of methylmalonic acidemia include: intellectual impairment (variable); tubulointerstitial nephritis with progressive renal failure; "metabolic stroke" (acute and chronic basal ganglia injury) causing a disabling movement disorder with choreoathetosis, dystonia, and para/quadriparesis; pancreatitis; growth failure; functional immune impairment; and optic nerve atrophy.
Vici syndrome
MedGen UID:
340962
Concept ID:
C1855772
Disease or Syndrome
Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012).
Endocardial fibroelastosis and coarctation of abdominal aorta
MedGen UID:
341665
Concept ID:
C1856971
Disease or Syndrome
Encephalopathy, axonal, with necrotizing myopathy, cardiomyopathy, and cataracts
MedGen UID:
341669
Concept ID:
C1856990
Disease or Syndrome
Yunis-Varon syndrome
MedGen UID:
341818
Concept ID:
C1857663
Disease or Syndrome
Yunis-Varon syndrome is a severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy (summary by Campeau et al., 2013).
Hemochromatosis type 3
MedGen UID:
388114
Concept ID:
C1858664
Disease or Syndrome
TFR2-related hereditary hemochromatosis (TFR2-HHC) is characterized by increased intestinal iron absorption resulting in iron accumulation in the liver, heart, pancreas, and endocrine organs. Age of onset is earlier than in HFE-associated HHC. The majority of individuals present with signs and symptoms of iron overload in the third decade (e.g., weakness, fatigue, abdominal pain, hepatomegaly, arthritis, arthralgia, progressive increase in skin pigmentation). Others present as young adults with nonspecific symptoms and abnormal serum iron studies or as adults with abnormal serum iron studies and signs of organ involvement including cirrhosis, diabetes mellitus, and arthropathy.
Cardiac lipidosis, familial
MedGen UID:
395234
Concept ID:
C1859332
Disease or Syndrome
Ataxia, deafness and cardiomyopathy
MedGen UID:
395312
Concept ID:
C1859645
Disease or Syndrome
Familial hypertrophic cardiomyopathy 7
MedGen UID:
348695
Concept ID:
C1860752
Disease or Syndrome
Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the TNNI3 gene.
Giant axonal neuropathy 2, autosomal dominant
MedGen UID:
400593
Concept ID:
C1864695
Disease or Syndrome
Giant axonal neuropathy-2 is an autosomal dominant peripheral axonal neuropathy characterized by onset of distal sensory impairment and lower extremity muscle weakness and atrophy after the second decade. Foot deformities may be present in childhood. More severely affected individuals may develop cardiomyopathy. Sural nerve biopsy shows giant axonal swelling with neurofilament accumulation (summary by Klein et al., 2014).
Hemochromatosis type 2A
MedGen UID:
356321
Concept ID:
C1865614
Disease or Syndrome
Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, glucose intolerance and diabetes, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has been reported occasionally. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.
Hemochromatosis type 2B
MedGen UID:
356040
Concept ID:
C1865616
Disease or Syndrome
Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, glucose intolerance and diabetes, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has been reported occasionally. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.
Peroxisome Biogenesis Disorder, Complementation Group 11
MedGen UID:
356213
Concept ID:
C1866351
Disease or Syndrome
Peroxisome biogenesis disorder, complementation group R
MedGen UID:
356512
Concept ID:
C1866352
Disease or Syndrome
Glycogen storage disease 0, muscle
MedGen UID:
409741
Concept ID:
C1969054
Disease or Syndrome
Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (hypoglycemia) after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and sugar levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure.\n\nThe signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0.\n\nGlycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired.
Familial restrictive cardiomyopathy 3
MedGen UID:
382807
Concept ID:
C2676271
Disease or Syndrome
Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).\n\nIn people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.\n\nAdults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis.\n\nFamilial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.
Familial hypertrophic cardiomyopathy 12
MedGen UID:
393755
Concept ID:
C2677491
Disease or Syndrome
Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the CSRP3 gene.
Refsum disease, adult, 2
MedGen UID:
440765
Concept ID:
C2749346
Disease or Syndrome
Amyloidogenic transthyretin amyloidosis
MedGen UID:
414031
Concept ID:
C2751492
Disease or Syndrome
Hereditary transthyretin (ATTR) amyloidosis is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy as well as non-neuropathic changes of cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis. The disease usually begins in the third to fifth decade in persons from endemic foci in Portugal and Japan; onset is later in persons from other areas. Typically, sensory neuropathy starts in the lower extremities with paresthesias and hypesthesias of the feet, followed within a few years by motor neuropathy. In some persons, particularly those with early-onset disease, autonomic neuropathy is the first manifestation of the condition; findings can include: orthostatic hypotension, constipation alternating with diarrhea, attacks of nausea and vomiting, delayed gastric emptying, sexual impotence, anhidrosis, and urinary retention or incontinence. Cardiac amyloidosis is mainly characterized by progressive cardiomyopathy. Individuals with leptomeningeal amyloidosis may have the following CNS findings: dementia, psychosis, visual impairment, headache, seizures, motor paresis, ataxia, myelopathy, hydrocephalus, or intracranial hemorrhage.
Emery-Dreifuss muscular dystrophy 5, autosomal dominant
MedGen UID:
414111
Concept ID:
C2751805
Disease or Syndrome
ALG1-CDG
MedGen UID:
419308
Concept ID:
C2931005
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) comprise a group of multisystem diseases with mostly severe psychomotor and mental retardation. Type I CDG comprises those disorders in which there are defects that affect biosynthesis of dolichol-linked oligosaccharides in the cytosol or the endoplasmic reticulum (ER), as well as defects involving the transfer of oligosaccharides onto nascent glycoproteins. Type II CDG comprises all defects of further trimming and elongation of N-linked oligosaccharides in the ER and Golgi (Schwarz et al., 2004). CDG1K is a type I CDG characterized by predominant neurologic involvement. Survival ranges from the second day of life to adulthood. The liver is affected in a minority of patients and shows hepatomegaly, edema, ascites, cholestatic jaundice, portal hypertension, and Budd-Chiari syndrome (summary by Marques-da-Silva et al., 2017). For a general discussion of CDGs, see CDG1A (212065).
Hermansky-Pudlak syndrome 1
MedGen UID:
419514
Concept ID:
C2931875
Disease or Syndrome
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.
Autosomal recessive limb-girdle muscular dystrophy type 2D
MedGen UID:
424706
Concept ID:
C2936332
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-3 affects mainly the proximal muscles and results in difficulty walking. Most individuals have onset in childhood; the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and contractures. Cardiomyopathy has rarely been reported (summary by Babameto-Laku et al., 2011). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1
MedGen UID:
461765
Concept ID:
C3150415
Disease or Syndrome
Congenital muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) are characterized by early onset of muscle weakness, usually before ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; Godfrey et al., 2007). Congenital muscular dystrophy-dystroglycanopathies with or without impaired intellectual development (type B) represent the intermediate range of the spectrum of dystroglycanopathies. They are less severe than muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and more severe than limb-girdle muscular dystrophy-dystroglycanopathy (type C; see MDDGC1, 609308). Genetic Heterogeneity of Congenital Muscular Dystrophy-Dystroglycanopathy with or without Impaired Intellectual Development (Type B) Congenital muscular dystrophy with impaired intellectual development due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGB2 (613156), caused by mutation in the POMT2 gene (607439); MDDGB3 (613151), caused by mutation in the POMGNT1 gene (606822); MDDGB4 (613152), caused by mutation in the FKTN gene (607440); MDDGB5 (616612), caused by mutation in the FKRP gene (606596); MDDGB6 (608840), caused by mutation in the LARGE gene (603590); MDDGB14 (615351), caused by mutation in the GMPPB gene (615320); and MDDGB15 (618992), caused by mutation in the DPM3 gene (605951).
D-2-hydroxyglutaric aciduria 2
MedGen UID:
462259
Concept ID:
C3150909
Disease or Syndrome
2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).\n\nThe main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.\n\nL-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.\n\nCombined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood.
Hypermethioninemia with s-adenosylhomocysteine hydrolase deficiency
MedGen UID:
462408
Concept ID:
C3151058
Disease or Syndrome
Hypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. This condition can occur when methionine is not broken down (metabolized) properly in the body.\n\nPeople with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.\n\nHypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia, and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula. The condition is called primary hypermethioninemia when it is not associated with other metabolic disorders or excess methionine in the diet.
Familial hypertrophic cardiomyopathy 17
MedGen UID:
462614
Concept ID:
C3151264
Disease or Syndrome
An autosomal dominant subtype of familial hypertrophic cardiomyopathy caused by mutation(s) in the JPH2 gene, encoding junctophilin-2.
Familial hypertrophic cardiomyopathy 18
MedGen UID:
462615
Concept ID:
C3151265
Disease or Syndrome
Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the PLN gene.
Familial hypertrophic cardiomyopathy 20
MedGen UID:
462617
Concept ID:
C3151267
Disease or Syndrome
Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the NEXN gene.
D-2-hydroxyglutaric aciduria 1
MedGen UID:
463405
Concept ID:
C3152055
Disease or Syndrome
D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, hypotonia, and dysmorphic features. Mild and severe phenotypes were characterized (van der Knaap et al., 1999). The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. The mild phenotype has a more variable clinical presentation. Genetic Heterogeneity of D-2-Hydroxyglutaric Aciduria D-2-hydroxyglutaric aciduria-2 (D2HGA2; 613657) is caused by heterozygous mutation in the mitochondrial isocitrate dehydrogenase-2 gene (IDH2; 147650) on chromosome 15q26.
Myopathy, distal, 4
MedGen UID:
481352
Concept ID:
C3279722
Disease or Syndrome
Williams distal myopathy is an autosomal dominant slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows nonspecific changes with no evidence of rods, necrosis, or inflammation (summary by Duff et al., 2011). Mutation in the FLNC gene can also cause myofibrillar myopathy-5 (MFM5; 609524), which shows a different pattern of muscle involvement and different histologic changes.
Hemochromatosis type 1
MedGen UID:
854011
Concept ID:
C3469186
Disease or Syndrome
HFE hemochromatosis is characterized by inappropriately high absorption of iron by the small intestinal mucosa. The phenotypic spectrum of HFE hemochromatosis includes: Persons with clinical HFE hemochromatosis, in whom manifestations of end-organ damage secondary to iron overload are present; Individuals with biochemical HFE hemochromatosis, in whom transferrin-iron saturation is increased and the only evidence of iron overload is increased serum ferritin concentration; and Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE hemochromatosis nor iron overload are present. Clinical HFE hemochromatosis is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and anterior pituitary gland. In untreated individuals, early symptoms include: abdominal pain, weakness, lethargy, weight loss, arthralgias, diabetes mellitus; and increased risk of cirrhosis when the serum ferritin is higher than 1,000 ng/mL. Other findings may include progressive increase in skin pigmentation, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE hemochromatosis is more common in men than women.
Familial hypertrophic cardiomyopathy 21
MedGen UID:
766356
Concept ID:
C3553442
Disease or Syndrome
Hypertrophic cardiomyopathy (CMH) is characterized by unexplained cardiac hypertrophy: thickening of the myocardial wall in the absence of any other identifiable cause for left ventricular hypertrophy such as systemic hypertension or valvular heart disease. Myocyte hypertrophy, disarray, and fibrosis are the histopathologic hallmarks of this disorder. Clinical features are diverse and include arrhythmias, sudden cardiac death, and heart failure. With an estimated prevalence of 1 in 500, CMH is the most common cardiovascular genetic disease and the most common cause of sudden death in competitive athletes in the United States (summary by Song et al., 2006). For a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600).
Combined oxidative phosphorylation deficiency 11
MedGen UID:
766981
Concept ID:
C3554067
Disease or Syndrome
COXPD11 is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes (summary by Garcia-Diaz et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2
MedGen UID:
767448
Concept ID:
C3554534
Disease or Syndrome
Mitochondrial complex IV deficiency nuclear type 6 (MC4DN6) is an autosomal recessive multisystem metabolic disorder with a highly variable phenotype. Some patients present in the neonatal period with encephalomyopathic features, whereas others present later in the first year of life with developmental regression. Manifestations include hypotonia, feeding difficulties, and global developmental delay. Many, but not all, patients develop hypertrophic cardiomyopathy, which may result in early death. Additional more variable features may include poor overall growth, microcephaly, seizures, neurodegeneration, spasticity, visual defects, retinopathy, and hepatic steatosis. Brain imaging in some patients shows features consistent with Leigh syndrome (see 256000). Laboratory studies show increased serum lactate and decreased levels and activity of mitochondrial respiratory complex IV (summary by Kennaway et al., 1990 and Oquendo et al., 2004). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
MedGen UID:
778253
Concept ID:
C3711645
Disease or Syndrome
Isolated deficiency of long-chain 3-hydroxyl-CoA dehydrogenase (LCHAD) is an autosomal recessive disorder characterized by early-onset cardiomyopathy, hypoglycemia, neuropathy, and pigmentary retinopathy, and sudden death (IJlst et al., 1996).
Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 14
MedGen UID:
811507
Concept ID:
C3714932
Disease or Syndrome
MDDGC14 is an autosomal recessive form of muscular dystrophy characterized by onset in early childhood of mild proximal muscle weakness. Some patients may have additional features, such as mild intellectual disability or seizures. It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Carss et al., 2013). Some patients with GMPPB mutations may show features consistent with a congenital myasthenic syndrome (see, e.g., CMS1A; 601462), such as fatigability and decremental compound muscle action potential response to repetitive nerve stimulation; these patients may show a positive therapeutic response to treatment with pyridostigmine (Belaya et al., 2015). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Myofibrillar myopathy 3
MedGen UID:
811509
Concept ID:
C3714934
Disease or Syndrome
Myofibrillar myopathy refers to a genetically heterogeneous group of muscular disorders characterized by a pathologic morphologic pattern of myofibrillar degradation and abnormal accumulation of proteins involved with the sarcomeric Z disc (summary by Foroud et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Infantile liver failure syndrome 2
MedGen UID:
815981
Concept ID:
C3809651
Disease or Syndrome
Infantile liver failure syndrome-2 is an autosomal recessive disorder characterized by recurrent episodes of acute liver failure during intercurrent febrile illness. Patients first present in infancy or early childhood, and there is complete recovery between episodes with conservative treatment (summary by Haack et al., 2015). For a discussion of genetic heterogeneity of infantile liver failure syndrome, see ILFS1 (615438).
Atrial standstill 2
MedGen UID:
816731
Concept ID:
C3810401
Disease or Syndrome
Atrial standstill (AS) is a rare condition characterized by the absence of electrical and mechanical activity in the atria. On surface ECG, AS is distinguished by bradycardia, junctional (usually narrow complex) escape rhythm, and absence of the P wave. Nearly 50% of patients with AS experience syncope. AS can be persistent or transient, and diffuse or partial (summary by Fazelifar et al., 2005).
Primary autosomal recessive microcephaly 13
MedGen UID:
863517
Concept ID:
C4015080
Disease or Syndrome
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay
MedGen UID:
863609
Concept ID:
C4015172
Disease or Syndrome
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013).
Combined oxidative phosphorylation deficiency 23
MedGen UID:
863884
Concept ID:
C4015447
Disease or Syndrome
Combined oxidative phosphorylation deficiency-23 is an autosomal recessive disorder characterized by early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development. Laboratory investigations are consistent with a defect in mitochondrial function resulting in lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Brain imaging shows abnormal lesions in the basal ganglia, thalamus, and brainstem. The severity of the disorder is variable, ranging from death in early infancy to survival into the second decade (summary by Kopajtich et al., 2014). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
MedGen UID:
897191
Concept ID:
C4225153
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+").
Spinal muscular atrophy with congenital bone fractures 1
MedGen UID:
896011
Concept ID:
C4225177
Disease or Syndrome
Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia with fetal hypokinesia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first days or months of life (summary by Knierim et al., 2016). Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone Fractures See also SMABF2 (616867), caused by mutation in the ASCC1 gene (614215) on chromosome 10q22.
Epileptic encephalopathy, early infantile, 35
MedGen UID:
904159
Concept ID:
C4225256
Disease or Syndrome
Developmental and epileptic encephalopathy-35 (DEE35) is an autosomal recessive neurodegenerative disorder characterized by onset of seizures in the first months of life associated with essentially no normal development. Brain imaging shows a characteristic pattern consistent with lack of myelination of early structures, including the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices. Many patients die in early childhood (summary by Kevelam et al., 2015) For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Klippel-feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism
MedGen UID:
894399
Concept ID:
C4225285
Disease or Syndrome
Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. Klippel-Feil anomaly is primarily defined by fusion of the cervical spine, with associated low posterior hairline and limited neck mobility being observed in about half of patients (summary by Alazami et al., 2015). For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Sialidosis type 2
MedGen UID:
924303
Concept ID:
C4282398
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency
MedGen UID:
934789
Concept ID:
C4310822
Disease or Syndrome
Lipid storage myopathy due to FLAD1 deficiency is an autosomal recessive inborn error of metabolism that includes variable mitochondrial dysfunction. The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment (summary by Olsen et al., 2016).
Nemaline myopathy 11, autosomal recessive
MedGen UID:
1384302
Concept ID:
C4479186
Disease or Syndrome
NEM11 is an autosomal recessive congenital myopathy characterized by onset of slowly progressive muscle weakness in the first decade. Affected individuals present with gait difficulties due to proximal muscle weakness and atrophy mainly affecting the lower limbs and neck. Muscle biopsy shows nemaline bodies. Some patients may have mild cardiac or respiratory involvement, but they do not have respiratory failure (summary by Miyatake et al., 2017). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800).
Somatotroph adenoma
MedGen UID:
1618709
Concept ID:
C4538355
Neoplastic Process
AIP familial isolated pituitary adenoma (AIP-FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and nonfunctioning pituitary adenomas (NFPA). Rarely TSH-secreting adenomas (thyrotropinomas) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-FIPA is usually in the second or third decade.
Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
MedGen UID:
1619876
Concept ID:
C4540192
Disease or Syndrome
NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding (summary by Wortmann et al., 2017).
Combined oxidative phosphorylation deficiency 33
MedGen UID:
1623699
Concept ID:
C4540209
Disease or Syndrome
COXPD33 is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. The phenotype is highly variable, ranging from death in infancy to adult-onset progressive external ophthalmoplegia (PEO) and myopathy. A common finding is cardiomyopathy and increased serum lactate (summary by Feichtinger et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Wolfram syndrome 1
MedGen UID:
1641635
Concept ID:
C4551693
Disease or Syndrome
WFS1 Wolfram syndrome spectrum disorder (WFS1-WSSD) is a progressive neurodegenerative disorder characterized by onset of diabetes mellitus (DM) and optic atrophy (OA) before age 16 years, and typically associated with other endocrine abnormalities, sensorineural hearing loss, and progressive neurologic abnormalities (cerebellar ataxia, peripheral neuropathy, dementia, psychiatric illness, and urinary tract atony). Although DM is mostly insulin-dependent, overall the course is milder (with lower prevalence of microvascular disease) than that seen in isolated DM. OA typically results in significantly reduced visual acuity in the first decade. Sensorineural hearing impairment ranges from congenital deafness to milder, sometimes progressive, hearing impairment.
Zimmermann-Laband syndrome 1
MedGen UID:
1639277
Concept ID:
C4551773
Disease or Syndrome
Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism, and abnormalities of the cartilage of the nose and/or ears (summary by Balasubramanian and Parker, 2010). Genetic Heterogeneity of Zimmermann-Laband Syndrome ZLS2 (616455) is caused by mutation in the ATP6V1B2 gene (606939) on chromosome 8p21. ZLS3 (618658) is caused by mutation in the KCNN3 gene (602983) on chromosome 1q21.
Myofibrillar myopathy, ZASP-related
MedGen UID:
1648314
Concept ID:
C4721886
Disease or Syndrome
A rare, genetic, non-dystrophic myofibrillar myopathy disorder characterized by late-adult onset of distal and/or proximal limb muscle weakness with initial involvement of posterior lower leg muscles, medial gastrocnemius and soleus. Patients present with ankle weakness followed by weakness of finger and wrist extensors and later on of proximal muscles. Ambulation is usually preserved. Late-onset associated cardiomyopathy and/or neuropathy has been reported in a minority of cases.
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2
MedGen UID:
1681210
Concept ID:
C5193026
Disease or Syndrome
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures, resulting in death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by Van Bergen et al., 2019). For a discussion of genetic heterogeneity of PEBEL, see PEBEL1 (617186).
Developmental and epileptic encephalopathy, 75
MedGen UID:
1684253
Concept ID:
C5193099
Disease or Syndrome
Developmental and epileptic encephalopathy-75 (DEE75) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by onset of severe refractory seizures in the first months of life. Patients often have global developmental delay before the onset of seizures, and thereafter achieve few milestones. EEG usually shows multifocal spikes and hypsarrhythmia, consistent with a clinical diagnosis of West syndrome. They have severely impaired intellectual development with inability to walk, absent speech, and hypotonia with axial hyperreflexia. Brain imaging shows progressive cerebral atrophy, frontal lobe atrophy, white matter abnormalities, and delayed myelination. Since the disorder is due to mitochondrial dysfunction, some patients may develop other organ involvement, including cardiomyopathy or liver and renal dysfunction. Death may occur in childhood (summary by Yin et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Combined oxidative phosphorylation deficiency 42
MedGen UID:
1709379
Concept ID:
C5394237
Disease or Syndrome
Combined oxidative phosphorylation deficiency-42 (COXPD42) is an autosomal recessive metabolic disorder characterized by onset of cardiomyopathy, respiratory insufficiency, lactic metabolic acidosis, and anemia in the first months of life. Patient tissue shows variable impairment of mitochondrial oxidative phosphorylation affecting mtDNA-encoded subunits I, III, and IV. All reported affected infants have died in the first year of life (summary by Friederich et al., 2018). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Mitochondrial complex 1 deficiency, nuclear type 35
MedGen UID:
1745427
Concept ID:
C5436576
Disease or Syndrome
Mitochondrial complex 4 deficiency, nuclear type 3
MedGen UID:
1764816
Concept ID:
C5436682
Disease or Syndrome
Familial ventricular tachycardia
MedGen UID:
83309
Concept ID:
C0340485
Disease or Syndrome
Scapulohumeral muscular dystrophy
MedGen UID:
98373
Concept ID:
C0410192
Disease or Syndrome
Limb-girdle muscular dystrophy, type 2J
MedGen UID:
324741
Concept ID:
C1837342
Disease or Syndrome
A form of limb-girdle muscular dystrophy that usually has a childhood onset (but can range from the first to third decade of life) of severe progressive proximal weakness, eventually involving the distal muscles. Some patients may remain ambulatory but most are wheelchair dependant 20 years after onset.
Tibial muscular dystrophy
MedGen UID:
333047
Concept ID:
C1838244
Disease or Syndrome
Udd distal myopathy – tibial muscular dystrophy (UDM-TMD) is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 30 years. Disease progression is slow and muscle weakness remains confined to the anterior compartment muscles for many years. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, UDM-TMD can remain unnoticed even in the elderly. EMG shows profound myopathic changes in the anterior tibial muscle, but preservation of the extensor brevis muscle. Muscle MRI shows selective fatty degeneration of the anterior tibial muscles and other anterior compartment muscles of the lower legs. Serum CK concentration may be normal or slightly elevated. Muscle biopsy shows progressive dystrophic changes in the tibialis anterior muscle with rimmed vacuoles at the early stages and replacement with adipose tissue at later stages of the disease.

Professional guidelines

PubMed

Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP; Heart Rhythm Society (HRS).; European Heart Rhythm Association (EHRA).
Europace 2011 Aug;13(8):1077-109. doi: 10.1093/europace/eur245. PMID: 21810866

Recent clinical studies

Etiology

Anghel L, Sascău R, Zota IM, Stătescu C
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115688. PMID: 34073616Free PMC Article
Kraus SM, Shaboodien G, Francis V, Laing N, Cirota J, Chin A, Pandie S, Lawrenson J, Comitis GAM, Fourie B, Zühlke L, Wonkam A, Wainwright H, Damasceno A, Mocumbi AO, Pepeta L, Moeketsi K, Thomas BM, Thomas K, Makotoko M, Brown S, Ntsekhe M, Sliwa K, Badri M, Gumedze F, Cordell HJ, Keavney B, Ferreira V, Mahmod M, Cooper LT, Yacoub M, Neubauer S, Watkins H, Mayosi BM, Ntusi NAB; IMHOTEP Investigators.
Int J Cardiol 2021 Jun 15;333:119-126. Epub 2021 Feb 16 doi: 10.1016/j.ijcard.2021.02.026. PMID: 33607192
Mizia-Stec K, Charron P, Gimeno Blanes JR, Elliott P, Kaski JP, Maggioni AP, Tavazzi L, Tendera M, Felix SB, Dominguez F, Ojrzynska N, Losi MA, Limongelli G, Barriales-Villa R, Seferovic PM, Biagini E, Wybraniec M, Laroche C, Caforio ALP; EORP Cardiomyopathy Registry Investigators.
Eur Heart J Cardiovasc Imaging 2021 Jun 22;22(7):781-789. doi: 10.1093/ehjci/jeaa329. PMID: 33417664Free PMC Article
Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Maggioni AP, Rubis PP, Jurcut R, Heliö T, Calò L, Sinagra G, Zdravkovic M, Olivotto I, Kavoliūnienė A, Laroche C, Caforio ALP, Charron P; Cardiomyopathy & Myocarditis Registry Investigators Group.
ESC Heart Fail 2021 Feb;8(1):95-105. Epub 2020 Nov 11 doi: 10.1002/ehf2.13100. PMID: 33179448Free PMC Article
Heliö T, Elliott P, Koskenvuo JW, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Mansencal N, Bilińska Z, Carr-White G, Damy T, Frustaci A, Kindermann I, Ripoll-Vera T, Čelutkienė J, Axelsson A, Lorenzini M, Saad A, Maggioni AP, Laroche C, Caforio ALP, Charron P; EORP Cardiomyopathy Registry Investigators Group.
ESC Heart Fail 2020 Oct;7(5):3013-3021. Epub 2020 Aug 7 doi: 10.1002/ehf2.12925. PMID: 32767651Free PMC Article

Diagnosis

Mizia-Stec K, Charron P, Gimeno Blanes JR, Elliott P, Kaski JP, Maggioni AP, Tavazzi L, Tendera M, Felix SB, Dominguez F, Ojrzynska N, Losi MA, Limongelli G, Barriales-Villa R, Seferovic PM, Biagini E, Wybraniec M, Laroche C, Caforio ALP; EORP Cardiomyopathy Registry Investigators.
Eur Heart J Cardiovasc Imaging 2021 Jun 22;22(7):781-789. doi: 10.1093/ehjci/jeaa329. PMID: 33417664Free PMC Article
Graziani F, Lillo R, Panaioli E, Spagnoletti G, Pieroni M, Ferrazzi P, Camporeale A, Verrecchia E, Sicignano LL, Manna R, Crea F
ESC Heart Fail 2021 Feb;8(1):725-728. Epub 2020 Nov 19 doi: 10.1002/ehf2.13101. PMID: 33211404Free PMC Article
Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Maggioni AP, Rubis PP, Jurcut R, Heliö T, Calò L, Sinagra G, Zdravkovic M, Olivotto I, Kavoliūnienė A, Laroche C, Caforio ALP, Charron P; Cardiomyopathy & Myocarditis Registry Investigators Group.
ESC Heart Fail 2021 Feb;8(1):95-105. Epub 2020 Nov 11 doi: 10.1002/ehf2.13100. PMID: 33179448Free PMC Article
Abozenah M, Kadado AJ, Aljamal A, Sawalha K, Salerno C, Battisha A, Hernandez-Montfort J, Lotfi A
Heart Lung 2021 Jul-Aug;50(4):546-557. Epub 2020 Nov 2 doi: 10.1016/j.hrtlng.2020.10.006. PMID: 33143911
Heliö T, Elliott P, Koskenvuo JW, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Mansencal N, Bilińska Z, Carr-White G, Damy T, Frustaci A, Kindermann I, Ripoll-Vera T, Čelutkienė J, Axelsson A, Lorenzini M, Saad A, Maggioni AP, Laroche C, Caforio ALP, Charron P; EORP Cardiomyopathy Registry Investigators Group.
ESC Heart Fail 2020 Oct;7(5):3013-3021. Epub 2020 Aug 7 doi: 10.1002/ehf2.12925. PMID: 32767651Free PMC Article

Therapy

Anghel L, Sascău R, Zota IM, Stătescu C
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115688. PMID: 34073616Free PMC Article
Huizar JF, Fisher SG, Ramsey FV, Kaszala K, Tan AY, Moore H, Koneru JN, Kron J, Padala SK, Ellenbogen KA, Singh SN
JACC Clin Electrophysiol 2021 Mar;7(3):380-390. Epub 2020 Nov 25 doi: 10.1016/j.jacep.2020.08.028. PMID: 33736756
Guo S, Guo Q
BMC Infect Dis 2021 Jan 7;21(1):33. doi: 10.1186/s12879-020-05722-z. PMID: 33413152Free PMC Article
Cui H, Schaff HV, Dearani JA, Lahr BD, Viehman JK, Geske JB, Nishimura RA, Ommen SR
J Thorac Cardiovasc Surg 2021 Mar;161(3):997-1006.e3. Epub 2020 Aug 25 doi: 10.1016/j.jtcvs.2020.08.066. PMID: 32977972
Yeung C, Mendoza I, Echeverria LE, Baranchuk A
Trends Cardiovasc Med 2021 May;31(4):233-239. Epub 2020 May 3 doi: 10.1016/j.tcm.2020.04.004. PMID: 32376493

Prognosis

Anghel L, Sascău R, Zota IM, Stătescu C
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115688. PMID: 34073616Free PMC Article
Kraus SM, Shaboodien G, Francis V, Laing N, Cirota J, Chin A, Pandie S, Lawrenson J, Comitis GAM, Fourie B, Zühlke L, Wonkam A, Wainwright H, Damasceno A, Mocumbi AO, Pepeta L, Moeketsi K, Thomas BM, Thomas K, Makotoko M, Brown S, Ntsekhe M, Sliwa K, Badri M, Gumedze F, Cordell HJ, Keavney B, Ferreira V, Mahmod M, Cooper LT, Yacoub M, Neubauer S, Watkins H, Mayosi BM, Ntusi NAB; IMHOTEP Investigators.
Int J Cardiol 2021 Jun 15;333:119-126. Epub 2021 Feb 16 doi: 10.1016/j.ijcard.2021.02.026. PMID: 33607192
Graziani F, Lillo R, Panaioli E, Spagnoletti G, Pieroni M, Ferrazzi P, Camporeale A, Verrecchia E, Sicignano LL, Manna R, Crea F
ESC Heart Fail 2021 Feb;8(1):725-728. Epub 2020 Nov 19 doi: 10.1002/ehf2.13101. PMID: 33211404Free PMC Article
Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Maggioni AP, Rubis PP, Jurcut R, Heliö T, Calò L, Sinagra G, Zdravkovic M, Olivotto I, Kavoliūnienė A, Laroche C, Caforio ALP, Charron P; Cardiomyopathy & Myocarditis Registry Investigators Group.
ESC Heart Fail 2021 Feb;8(1):95-105. Epub 2020 Nov 11 doi: 10.1002/ehf2.13100. PMID: 33179448Free PMC Article
Kitaoka H, Kubo T, Doi YL
Circ J 2020 Jul 22;84(8):1218-1226. Epub 2020 Jul 14 doi: 10.1253/circj.CJ-20-0524. PMID: 32669480

Clinical prediction guides

Anghel L, Sascău R, Zota IM, Stătescu C
Int J Mol Sci 2021 May 26;22(11) doi: 10.3390/ijms22115688. PMID: 34073616Free PMC Article
Kim M, Lu L, Dvornikov AV, Ma X, Ding Y, Zhu P, Olson TM, Lin X, Xu X
Int J Mol Sci 2021 May 23;22(11) doi: 10.3390/ijms22115494. PMID: 34071043Free PMC Article
Graziani F, Lillo R, Panaioli E, Spagnoletti G, Pieroni M, Ferrazzi P, Camporeale A, Verrecchia E, Sicignano LL, Manna R, Crea F
ESC Heart Fail 2021 Feb;8(1):725-728. Epub 2020 Nov 19 doi: 10.1002/ehf2.13101. PMID: 33211404Free PMC Article
Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M, Kaski JP, Maggioni AP, Rubis PP, Jurcut R, Heliö T, Calò L, Sinagra G, Zdravkovic M, Olivotto I, Kavoliūnienė A, Laroche C, Caforio ALP, Charron P; Cardiomyopathy & Myocarditis Registry Investigators Group.
ESC Heart Fail 2021 Feb;8(1):95-105. Epub 2020 Nov 11 doi: 10.1002/ehf2.13100. PMID: 33179448Free PMC Article
Kitaoka H, Kubo T, Doi YL
Circ J 2020 Jul 22;84(8):1218-1226. Epub 2020 Jul 14 doi: 10.1253/circj.CJ-20-0524. PMID: 32669480

Recent systematic reviews

Kamp NJ, Chery G, Kosinski AS, Desai MY, Wazni O, Schmidler GS, Patel M, Lopes RD, Morin DP, Al-Khatib SM
Prog Cardiovasc Dis 2021 May-Jun;66:10-16. Epub 2020 Nov 7 doi: 10.1016/j.pcad.2020.11.001. PMID: 33171204
Chadalawada S, Sillau S, Archuleta S, Mundo W, Bandali M, Parra-Henao G, Rodriguez-Morales AJ, Villamil-Gomez WE, Suárez JA, Shapiro L, Hotez PJ, Woc-Colburn L, DeSanto K, Rassi A Jr, Franco-Paredes C, Henao-Martínez AF
JAMA Netw Open 2020 Aug 3;3(8):e2015072. doi: 10.1001/jamanetworkopen.2020.15072. PMID: 32865573Free PMC Article
Siskind D, Sidhu A, Cross J, Chua YT, Myles N, Cohen D, Kisely S
Aust N Z J Psychiatry 2020 May;54(5):467-481. Epub 2020 Jan 20 doi: 10.1177/0004867419898760. PMID: 31957459
Rong SL, Wang ZK, Zhou XD, Wang XL, Yang ZM, Li B
J Transl Med 2019 Jul 11;17(1):221. doi: 10.1186/s12967-019-1966-4. PMID: 31296244Free PMC Article
Eschenhagen T, Carrier L
Pflugers Arch 2019 May;471(5):755-768. Epub 2018 Oct 15 doi: 10.1007/s00424-018-2214-0. PMID: 30324321Free PMC Article

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