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Constipation

MedGen UID:
368096
Concept ID:
C1963087
Finding
Synonyms: Costiveness; Dyschezia
 
HPO: HP:0002019

Conditions with this feature

Lipomatosis dolorosa
MedGen UID:
1757
Concept ID:
C0001529
Disease or Syndrome
Adiposis dolorosa, also known as Dercum disease, is characterized by generalized obesity and pronounced, disabling, and chronic pain in the adipose tissue of the proximal extremities, trunk, pelvic area, and buttocks; the face and hands are usually spared. There are a number of associated symptoms, including multiple lipomas, generalized weakness, fatigue, sleep disturbances, constipation, and psychiatric abnormalities. It is 5 to 30 times more common in women than men, and usually presents between 35 and 50 years of age (summary by Campen et al., 2001; review by Hansson et al., 2012). Based on a review of the literature and studies of 111 patients, Hansson et al. (2012) proposed a classification of Dercum disease into 4 types: (I) generalized diffuse form without clear lipomas, (II) generalized nodular form with multiple lipomas, (III) localized nodular form, and (IV) juxtaarticular form with solitary fatty deposits near joints.
Familial dysautonomia
MedGen UID:
41678
Concept ID:
C0013364
Congenital Abnormality
Familial dysautonomia (FD) affects the development and survival of sensory, sympathetic, and parasympathetic neurons. It is a debilitating disease present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temperature perception, and cardiovascular instability. About 40% of individuals have autonomic crises. Hypotonia contributes to delay in acquisition of motor milestones. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Life expectancy is decreased.
Primary erythromelalgia
MedGen UID:
8688
Concept ID:
C0014805
Disease or Syndrome
SCN9A-related inherited erythromelalgia (SCN9A-related IEM) is characterized by recurrent attacks of bilateral and symmetric intense pain, redness, warmth, and swelling involving the feet and, less frequently, the hands. SCN9A-related IEM is not associated with an organic disease. Manifestations may vary within a family. Onset is usually in childhood or adolescence but has been recognized in infants and adults. At onset, episodes are triggered by warmth; other precipitating factors include: exercise, tight shoes, wearing socks, alcohol, spicy foods, and other vasodilating agents. In advanced disease, symptoms may occur many times a day or become constant. Some individuals have allodynia (pain evoked by a normally innocuous stimulus) and hyperalgesia (increased sensitivity to a painful stimulus). Episodes may be disabling, interfere with sleep, and severely limit normal activities such as walking, participation in sports, wearing socks and shoes, and attending school or going to work.
Pigmentary pallidal degeneration
MedGen UID:
6708
Concept ID:
C0018523
Disease or Syndrome
Pantothenate kinase-associated neurodegeneration (PKAN) is a form of neurodegeneration with brain iron accumulation, or NBIA (formerly called Hallervorden-Spatz syndrome). PKAN is characterized by progressive dystonia and basal ganglia iron deposition with onset that usually occurs before age ten years. Commonly associated features include dysarthria, rigidity, and pigmentary retinopathy. Approximately 25% of affected individuals have an 'atypical' presentation with later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.
Multiple endocrine neoplasia, type 2b
MedGen UID:
9959
Concept ID:
C0025269
Neoplastic Process
Multiple endocrine neoplasia type 2 (MEN 2) is classified into three subtypes: MEN 2A, FMTC (familial medullary thyroid carcinoma), and MEN 2B. All three subtypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN 2A and MEN 2B have an increased risk for pheochromocytoma; MEN 2A has an increased risk for parathyroid adenoma or hyperplasia. Additional features in MEN 2B include mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and a ‘marfanoid’ habitus. MTC typically occurs in early childhood in MEN 2B, early adulthood in MEN 2A, and middle age in FMTC.
Myxedema
MedGen UID:
6506
Concept ID:
C0027145
Disease or Syndrome
A condition characterized by a dry, waxy type of swelling (EDEMA) with abnormal deposits of MUCOPOLYSACCHARIDES in the SKIN and other tissues. It is caused by a deficiency of THYROID HORMONES. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips.
Lowe syndrome
MedGen UID:
18145
Concept ID:
C0028860
Disease or Syndrome
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, aminoaciduria, low molecular-weight (LMW) proteinuria, sodium and potassium wasting, and polyuria. Fanconi syndrome is usually not clinically apparent in the first few months of life, but symptoms may appear by age six to 12 months. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease after age ten to 20 years.
Prune belly syndrome
MedGen UID:
18718
Concept ID:
C0033770
Congenital Abnormality
In its rare complete form, 'prune belly' syndrome comprises megacystis (massively enlarged bladder) with disorganized detrusor muscle, cryptorchidism, and thin abdominal musculature with overlying lax skin (summary by Weber et al., 2011).
Rett disorder
MedGen UID:
48441
Concept ID:
C0035372
Disease or Syndrome
MECP2-related disorders in females include classic Rett syndrome, variant Rett syndrome, and mild learning disabilities. A pathogenic MECP2 variant in a male is presumed to most often be lethal; phenotypes in rare surviving males are primarily severe neonatal encephalopathy and manic-depressive psychosis, pyramidal signs, Parkinsonian, and macro-orchidism (PPM-X syndrome). Classic Rett syndrome, a progressive neurodevelopmental disorder primarily affecting girls, is characterized by apparently normal psychomotor development during the first six to 18 months of life, followed by a short period of developmental stagnation, then rapid regression in language and motor skills, followed by long-term stability. During the phase of rapid regression, repetitive, stereotypic hand movements replace purposeful hand use. Additional findings include fits of screaming and inconsolable crying, autistic features, panic-like attacks, bruxism, episodic apnea and/or hyperpnea, gait ataxia and apraxia, tremors, seizures, and acquired microcephaly. Atypical Rett syndrome is observed increasingly as MECP2 variants are identified in individuals previously diagnosed with: clinically suspected but molecularly unconfirmed Angelman syndrome; intellectual disability with spasticity or tremor; mild learning disability; or (rarely) autism. Severe neonatal encephalopathy resulting in death before age two years is the most common phenotype observed in affected males.
Rubinstein-Taybi syndrome
MedGen UID:
48517
Concept ID:
C0035934
Disease or Syndrome
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.
Werdnig-Hoffmann disease
MedGen UID:
21913
Concept ID:
C0043116
Disease or Syndrome
Spinal muscular atrophy (SMA) is characterized by progressive muscle weakness resulting from degeneration and loss of the anterior horn cells (i.e., lower motor neurons) in the spinal cord and the brain stem nuclei. Onset ranges from before birth to adolescence or young adulthood. Poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint contractures are common complications. Before the genetic basis of SMA was understood, it was classified into clinical subtypes; however, it is now apparent that the phenotype of SMA associated with disease-causing mutations of SMN1 spans a continuum without clear delineation of subtypes. Nonetheless, classification by age of onset and maximum function achieved is useful for prognosis and management; subtypes include: SMA 0 (proposed), with prenatal onset and severe joint contractures, facial diplegia, and respiratory failure; SMA I, with onset before age six months; SMA II, with onset between age six and 12 months; SMA III, with onset in childhood after age 12 months and ability to walk at least 25 meters achieved; and SMA IV, with adult onset.
Epidermolysis bullosa herpetiformis, Dowling-Meara
MedGen UID:
38194
Concept ID:
C0079295
Disease or Syndrome
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some cases) that results in nonscarring blisters caused by little or no trauma. The current classification of epidermolysis bullosa (EB) includes two major types and 12 minor subtypes of EBS; all share the common feature of blistering above the dermal-epidermal junction at the ultrastructural level. The four most common subtypes of EBS are the focus of this GeneReview: EBS, localized (EBS-loc; previously known as Weber-Cockayne type). EBS, Dowling-Meara type (EBS-DM). EBS, other generalized (EBS, gen-nonDM; previously known as Koebner type). EBS-with mottled pigmentation (EBS-MP). The phenotypes for these subtypes range from relatively mild blistering of the hands and feet to more generalized blistering, which can be fatal. In EBS-loc, blisters are rarely present or minimal at birth and may occur on the knees and shins with crawling or on the feet at approximately age18 months; some individuals manifest the disease in adolescence or early adulthood. Blisters are usually confined to the hands and feet, but can occur anywhere if trauma is significant. In EBS, gen-non DM, blisters may be present at birth or develop within the first few months of life. Involvement is more widespread than in EBS-loc, but generally milder than in EBS-DM. In EBS-MP, skin fragility is evident at birth and clinically indistinguishable from EBS-DM; over time, progressive brown pigmentation interspersed with hypopigmented spots develops on the trunk and extremities, with the pigmentation disappearing in adult life. Focal palmar and plantar hyperkeratoses may occur. In EBS-DM, onset is usually at birth; severity varies greatly, both within and among families. Widespread and severe blistering and/or multiple grouped clumps of small blisters are typical and hemorrhagic blisters are common. Improvement occurs during mid- to late childhood. EBS-DM appears to improve with warmth in some individuals. Progressive hyperkeratosis of the palms and soles begins in childhood and may be the major complaint of affected individuals in adult life. Nail dystrophy and milia are common. Both hyper- and hypopigmentation can occur. Mucosal involvement in EBS-DM may interfere with feeding. Blistering can be severe enough to result in neonatal or infant death.
Recessive dystrophic epidermolysis bullosa
MedGen UID:
36311
Concept ID:
C0079474
Disease or Syndrome
Dystrophic epidermolysis bullosa (DEB) comprises two types based on inheritance pattern: Recessive DEB, including severe generalized (RDEB-sev gen; formerly called Hallopeau-Siemens type [RDEB-HS]) and generalized other (RDEB-O; formerly called non-Hallopeau-Siemens type [RDEB-non-HS]). Dominant DEB (DDEB). In RDEB-sev gen, blisters affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, severe nutritional deficiency and secondary problems are common. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, a hallmark of this disorder. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB-O may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the severe, mutilating scarring seen in RDEB-sev gen. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Hereditary coproporphyria
MedGen UID:
57931
Concept ID:
C0162531
Disease or Syndrome
Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. Attacks typically start in the abdomen with low-grade pain that slowly increases over a period of days (not hours) with nausea progressing to vomiting. In some individuals, the pain is predominantly in the back or extremities. When an acute attack is untreated, a motor neuropathy may develop over a period of days or a few weeks. The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Some individuals experience respiratory insufficiency due to loss of innervation of the diaphragm and muscles of respiration. Acute attacks are associated commonly with use of certain medications, caloric deprivation, and changes in female reproductive hormones. About 20% of those with an acute attack also experience photosensitivity associated with bullae and skin fragility.
Variegate porphyria
MedGen UID:
58118
Concept ID:
C0162532
Disease or Syndrome
Variegate porphyria is characterized by cutaneous manifestations, including increased photosensitivity, blistering, skin fragility with chronic scarring of sun-exposed areas, and postinflammatory hyperpigmentation. Acute exacerbations of VP include abdominal pain, the passage of dark urine, and neuropsychiatric symptoms that characterize the acute hepatic porphyrias, such as bulbar paralysis, quadriplegia, motor neuropathy, and weakness of the limbs. In heterozygotes, PPOX activity is decreased by about 50% (summary by Frank et al., 1998).
Acute intermittent porphyria
MedGen UID:
56452
Concept ID:
C0162565
Disease or Syndrome
Acute intermittent porphyria (referred to as AIP in this GeneReview) results from half-normal activity of the enzyme hydroxymethylbilane synthase (HMBS). It is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal pain without peritoneal signs, often accompanied by nausea, vomiting, tachycardia, and hypertension. Attacks may be complicated by neurologic findings (mental changes, convulsions, and peripheral neuropathy that may progress to respiratory paralysis), and hyponatremia. Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, and infections, usually resolve within two weeks. Most individuals with AIP have one or a few attacks; about 5% (mainly women) have recurrent attacks (defined as >4 attacks/year) that may persist for years. Other long-term complications are chronic renal failure, hepatocellular carcinoma (HCC), and hypertension. Attacks, which are very rare before puberty, are more common in women than men. All individuals with a genetic change in the gene HMBS that predisposes to AIP are at risk of developing acute attacks; however, most never have symptoms and are said to have latent (or presymptomatic) AIP.
Angelman syndrome
MedGen UID:
58144
Concept ID:
C0162635
Disease or Syndrome
Angelman syndrome (AS) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. Developmental delays are first noted at around age six months; however, the unique clinical features of AS do not become manifest until after age one year, and it can take several years before the correct clinical diagnosis is obvious.
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke
MedGen UID:
56485
Concept ID:
C0162671
Disease or Syndrome
MELAS syndrome, comprising mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with a variable clinical phenotype. The disorder is accompanied by features of central nervous system involvement, including seizures, hemiparesis, hemianopsia, cortical blindness, and episodic vomiting (Pavlakis et al., 1984; Montagna et al., 1988). Other mitochondrial encephalomyopathies include Leigh syndrome (LS; 256000), Kearns-Sayre syndrome (KSS; 530000), MERRF syndrome (545000), and Leber optic atrophy (535000).
Smith-Lemli-Opitz syndrome
MedGen UID:
61231
Concept ID:
C0175694
Disease or Syndrome
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide and individuals have been described with normal development and only minor malformations.
Williams syndrome
MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to failure to thrive in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.
Aicardi syndrome
MedGen UID:
61236
Concept ID:
C0175713
Disease or Syndrome
Aicardi syndrome was classically characterized by a triad of features: agenesis of the corpus callosum, distinctive chorioretinal lacunae, and infantile spasms. However, it is now well recognized that several other important findings are typically present in girls with Aicardi syndrome. Neurologic examination can reveal microcephaly, axial hypotonia, and appendicular hypertonia with spasticity. Moderate to severe global developmental delay and intellectual disability are expected. Many girls with Aicardi syndrome develop seizures prior to age three months, and most before age one year. Ongoing medically refractory epilepsy with a variety of seizure types develops over time. Costovertebral defects are common and can lead to marked scoliosis in up to one third of affected individuals. Other features include characteristic facial features, gastrointestinal difficulties, small hands, vascular malformations and pigmentary lesions of the skin, increased incidence of tumors, lower growth rate after ages seven to nine years, and precocious or delayed puberty. Survival is highly variable, with the mean age of death about 8.3 years and the median age of death about 18.5 years.
Fatal familial insomnia
MedGen UID:
104768
Concept ID:
C0206042
Disease or Syndrome
Genetic prion diseases generally manifest with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Note: A fourth clinical phenotype, known as Huntington disease like-1 (HDL-1) has been proposed, but this is based on a single report, and the underlying pathologic features would categorize it as GSS. Although it is clear that these four subtypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset ranges from the third to ninth decade of life. The course ranges from a few months to several years (typically 5-7 years; in rare instances, >10 years).
FG syndrome
MedGen UID:
113106
Concept ID:
C0220769
Disease or Syndrome
The phenotypic spectrum of MED12-related disorders, which is still being defined, includes at a minimum the phenotypes of FG syndrome type 1 (FGS1) and Lujan syndrome (LS). FGS1 and LS share the clinical findings of cognitive impairment, hypotonia, and abnormalities of the corpus callosum. FGS1 is further characterized by absolute or relative macrocephaly, tall forehead, downslanted palpebral fissures, small and simple ears, constipation and/or anal anomalies, broad thumbs and halluces, and characteristic behavior. LS is further characterized by large head, tall thin body habitus, long thin face, high nasal root, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected.
Hypothalamic hypothyroidism
MedGen UID:
113137
Concept ID:
C0220998
Disease or Syndrome
Pseudoprimary hyperaldosteronism
MedGen UID:
67439
Concept ID:
C0221043
Disease or Syndrome
Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension, hypokalemia, metabolic alkalosis, and suppression of plasma renin activity and aldosterone secretion (summary by Yang et al., 2014).
Volvulus of midgut
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
A congenital abnormality in which the intestine is abnormally rotated (twisted). It may result in intestinal obstruction.
Gastrointestinal Stromal Tumors
MedGen UID:
116049
Concept ID:
C0238198
Neoplastic Process
Gastrointestinal stromal tumors are mesenchymal tumors found in the gastrointestinal tract that originate from the interstitial cells of Cajal, the pacemaker cells that regulate peristalsis in the digestive tract. Approximately 70% of GISTs develop in the stomach, 20% in the small intestine, and less than 10% in the esophagus, colon, and rectum. GISTs are typically more cellular than other gastrointestinal sarcomas. They occur predominantly in patients who are 40 to 70 years old but in rare cases may occur in younger persons (Miettinen et al., 1999, 1999). GISTs can also be seen in neurofibromatosis-1 (NF1; 162200) due to mutations in the NF1 gene, and are thus distinct from the GISTs described here. Sandberg and Bridge (2002) reviewed the cytogenetics and molecular genetics of gastrointestinal stromal tumors. Coffey et al. (2007) reviewed the clinical features, pathogenesis, and molecular treatments of Menetrier disease (137280) and GIST, both of which are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases.
Townes syndrome
MedGen UID:
75555
Concept ID:
C0265246
Disease or Syndrome
Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.
Turcot syndrome
MedGen UID:
78553
Concept ID:
C0265325
Disease or Syndrome
Lynch syndrome, caused by a germline pathogenic variant in a mismatch repair gene and associated with tumors exhibiting microsatellite instability (MSI), is characterized by an increased risk for colon cancer and cancers of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following life time risks for cancer are seen: 52%-82% for colorectal cancer (mean age at diagnosis 44-61 years); 25%-60% for endometrial cancer in women (mean age at diagnosis 48-62 years); 6% to 13% for gastric cancer (mean age at diagnosis 56 years); and 4%-12% for ovarian cancer (mean age at diagnosis 42.5 years; approximately 30% are diagnosed before age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.
Niemann-Pick disease, type A
MedGen UID:
78650
Concept ID:
C0268242
Disease or Syndrome
Acid sphingomyelinase (ASM) deficiency has been categorized in the past as either neuronopathic (Niemann-Pick disease type A [NPD-A]), with death in early childhood, or non-neuronopathic (Niemann-Pick disease type B [NPD-B]). While forms intermediate to these two extremes occur, all ASM deficiency that is not NPD-A is designated in this review as NPD-B, despite its wide range of manifestations and severity. The first symptom in NPD-A is hepatosplenomegaly, usually noted by age three months; over time the liver and spleen become massive. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year. NPD type B, later in onset and milder in manifestations than NPD type A, is characterized by hepatosplenomegaly with progressive hypersplenism and stable liver dysfunction, gradual deterioration in pulmonary function, osteopenia, and atherogenic lipid profile. Progressive and/or clinically significant neurologic manifestations occur infrequently. Survival to adulthood can occur.
Ehlers-Danlos syndrome, type 3
MedGen UID:
75670
Concept ID:
C0268337
Disease or Syndrome
Ehlers-Danlos syndrome (EDS), hypermobility type is generally considered the least severe type of EDS, although significant complications, primarily musculoskeletal, can and do occur. The skin is often soft or velvety and may be mildly hyperextensible. Subluxations and dislocations are common; they may occur spontaneously or with minimal trauma and can be acutely painful. Degenerative joint disease is common. Chronic pain, distinct from that associated with acute dislocations, is a serious complication of the condition and can be both physically and psychologically disabling. Easy bruising is common. Functional bowel disorders are likely underrecognized. Autonomic dysfunction, such as orthostatic intolerance, may also be seen. Aortic root dilation is typically of a mild degree with no increased risk of dissection in the absence of significant dilation. Psychological dysfunction, psychosocial impairment, and emotional problems are common.
Infantile hypophosphatasia
MedGen UID:
75677
Concept ID:
C0268412
Disease or Syndrome
Hypophosphatasia is characterized by defective mineralization of bone and/or teeth in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. At least six clinical forms are currently recognized based on age at diagnosis and severity of features: Perinatal (lethal) hypophosphatasia characterized by respiratory insufficiency and hypercalcemia. Perinatal (benign) hypophosphatasia with prenatal skeletal manifestations that slowly resolve into the milder childhood or adult form. Infantile hypophosphatasia with onset between birth and age six months of rickets without elevated serum alkaline phosphatase activity. Childhood hypophosphatasia that ranges from low bone mineral density for age with unexplained fractures to rickets. Adult hypophosphatasia characterized by early loss of adult dentition and stress fractures and pseudofractures of the lower extremities in middle age. Odontohypophosphatasia characterized by premature exfoliation of primary teeth and/or severe dental caries as an isolated finding or as part of the above forms of hypophosphatasia.
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 poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, coma, and death. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Late-onset PA includes developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction (resulting in dystonia and choreoathetosis) and cardiomyopathy. Affected children can have an acute decompensation that resembles the neonatal presentation and is precipitated by a catabolic stress such as infection, injury, or surgery. Isolated cardiomyopathy and arrhythmia 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 (POI), and chronic renal failure.
Alexander disease
MedGen UID:
78724
Concept ID:
C0270726
Disease or Syndrome
Alexander disease is a progressive disorder of cerebral white matter that predominantly affects infants and children and has variable life expectancy. The later-onset forms present with a slower clinical course. The infantile form comprises about 42% of affected individuals, the juvenile form about 22%, and the adult form about 33%. A neonatal form is also recognized. The neonatal form leads to severe disability or death within two years. Characteristics include seizures, hydrocephalus, severe motor and intellectual disability, and elevated CSF protein concentration. MRI shows severe white matter abnormalities with involvement of the basal ganglia and cerebellum. The infantile form presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly, frontal bossing, and seizures. Other findings include hyperreflexia and pyramidal signs, ataxia, and occasional hydrocephalus secondary to aqueductal stenosis. Affected children survive weeks to several years. The juvenile form usually presents between ages four and ten years, occasionally in the mid-teens. Findings can include bulbar/pseudobulbar signs, ataxia, gradual loss of intellectual function, seizures, normocephaly or megalencephaly, and breathing problems. Survival ranges from the early teens to the 20s-30s. The adult form is the most variable.
Secondary hypothyroidism
MedGen UID:
78786
Concept ID:
C0271789
Disease or Syndrome
Septo-optic dysplasia sequence
MedGen UID:
90926
Concept ID:
C0338503
Congenital Abnormality
Septooptic dysplasia is a clinically heterogeneous disorder loosely defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum (Dattani et al., 1998). The diagnosis of this rare congenital anomaly is made when 2 or more features of the classic triad are present. Approximately 30% of patients have complete manifestations, 62% display hypopituitarism, and 60% have an absent septum pellucidum. The disorder is equally prevalent in males and females and is more common in infants born to younger mothers, with a reported incidence of 1 in 10,000 live births (summary by Webb and Dattani, 2010). Also see 516020.0012 for a form of septooptic dysplasia associated with cardiomyopathy and exercise intolerance.
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Congenital Abnormality
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 malonyl-CoA decarboxylase
MedGen UID:
91001
Concept ID:
C0342793
Disease or Syndrome
Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).
Ochoa syndrome
MedGen UID:
98015
Concept ID:
C0403555
Disease or Syndrome
Urofacial syndrome (UFS) is characterized by prenatal or infantile onset of urinary bladder voiding dysfunction, abnormal facial movement with expression (resulting from abnormal co-contraction of the corners of the mouth and eyes), and often bowel dysfunction (constipation and/or encopresis). Bladder voiding dysfunction increases the risk for urinary incontinence, megacystis, vesicoureteric reflux, hydroureteronephrosis, urosepsis, and progressive renal impairment.
Floating-Harbor syndrome
MedGen UID:
152667
Concept ID:
C0729582
Disease or Syndrome
Floating-Harbor syndrome is a rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips (Lacombe et al., 1995). Rubinstein-Taybi syndrome (see 180849), which shows phenotypic overlap with Floating-Harbor syndrome, is caused by mutation in the CREBBP gene (600140), for which SRCAP is a coactivator.
Chromosome 9q deletion syndrome
MedGen UID:
208639
Concept ID:
C0795833
Disease or Syndrome
Kleefstra syndrome is characterized by intellectual disability, childhood hypotonia, and distinctive facial features. The majority of individuals function in the moderate to severe spectrum of intellectual disability although a few individuals have mild delay and total IQ around 70. Although most have severe expressive speech delay with little speech development, general language development is usually at a higher level, making nonverbal communication possible. A complex pattern of other findings can also be observed including heart defects, renal/urologic defects, genital defects in males, severe respiratory infections, epilepsy/febrile seizures, autistic-like features in childhood, and extreme apathy or catatonic-like features after puberty.
11q partial monosomy syndrome
MedGen UID:
162878
Concept ID:
C0795841
Disease or Syndrome
Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder. The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorders, which are characterized by impaired communication and socialization skills. Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cell fragments that are necessary for blood clotting. Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.
Smith-Magenis syndrome
MedGen UID:
162881
Concept ID:
C0795864
Disease or Syndrome
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly facial features that progress with age), developmental delay, cognitive impairment, and behavioral abnormalities. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory integration issues are frequently noted. Children and adults typically have inattention, distractibility, hyperactivity, impulsivity, maladaptive behaviors including frequent outbursts/temper tantrums, attention seeking, disobedience, aggression, toileting difficulties, and self-injurious behaviors (SIB) including self-hitting, self-biting, and/or skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. The finger lick and page flipping ("lick and flip") behavior may be less prevalent than initially reported. An underlying developmental asynchrony, specifically between intellectual functioning and emotional maturity, may also contribute to maladaptive behaviors in people with SMS.
Mental retardation-hypotonic facies syndrome X-linked, 1
MedGen UID:
167093
Concept ID:
C0796003
Disease or Syndrome
The term 'X-linked mental retardation-hypotonic facies syndrome' comprises several syndromes previously reported separately. These include Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, and Smith-Fineman-Myers syndromes as well as 1 family with X-linked mental retardation with spastic paraplegia. All these syndromes were found to be caused by mutation in the XH2 gene and are characterized primarily by severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women (Abidi et al., 2005). Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects. X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is an allelic disorder with a similar phenotype with the addition of alpha-thalassemia and Hb H inclusion bodies in erythrocytes.
Kapur Toriello syndrome
MedGen UID:
208654
Concept ID:
C0796005
Disease or Syndrome
Retarded mental and growth development with variable congenial defects, including heart abnormalities, intestinal malrotation, characteristic facies, and other anomalies.
C syndrome
MedGen UID:
167105
Concept ID:
C0796095
Disease or Syndrome
The C syndrome, also known as Opitz trigonocephaly syndrome, is a malformation syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears (summary by Kaname et al., 2007). C syndrome shows phenotypic overlap with Bohring-Opitz syndrome, or C-like syndrome (605039), a disorder with more severe features than C syndrome, caused by heterozygous mutation in the ASXL1 gene (612990) on chromosome 20q11.
Myoneural gastrointestinal encephalopathy syndrome
MedGen UID:
167876
Concept ID:
C0872218
Disease or Syndrome
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility (manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea); cachexia; ptosis/ophthalmoplegia or ophthalmoparesis; leukoencephalopathy; and demyelinating peripheral neuropathy (manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities). The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years.
Cardiofaciocutaneous syndrome
MedGen UID:
266149
Concept ID:
C1275081
Disease or Syndrome
Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances), distinctive craniofacial appearance, and cutaneous abnormalities (including xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas, and palmoplantar hyperkeratosis). The hair is typically sparse, curly, fine or thick, woolly or brittle; eyelashes and eyebrows may be absent or sparse. Nails may be dystrophic or fast growing. Some form of neurologic and/or cognitive delay (ranging from mild to severe) is seen in all affected individuals. Neoplasia, mostly acute lymphoblastic leukemia (ALL), has been reported in some individuals.
TNF receptor-associated periodic fever syndrome (TRAPS)
MedGen UID:
226899
Concept ID:
C1275126
Congenital Abnormality
Tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes. During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis. The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in early childhood.
Deficiency of aromatic-L-amino-acid decarboxylase
MedGen UID:
220945
Concept ID:
C1291564
Disease or Syndrome
AADC deficiency is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (Abeling et al., 2000). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by Brun et al., 2010).
Nephrogenic diabetes insipidus, X-linked
MedGen UID:
288785
Concept ID:
C1563705
Disease or Syndrome
Nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals.
Nephrogenic diabetes insipidus, autosomal
MedGen UID:
289643
Concept ID:
C1563706
Disease or Syndrome
Nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals.
Thyroid agenesis
MedGen UID:
289647
Concept ID:
C1563716
Disease or Syndrome
In 80 to 85% of cases, congenital hypothyroidism is associated with, and presumably is a consequence of, thyroid dysgenesis (Macchia et al., 1998). In these cases, the thyroid gland can be absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia). When thyroid hormone therapy is not initiated within the first 2 months of life, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (cretinism).
Myofibrillar myopathy 1
MedGen UID:
330449
Concept ID:
C1832370
Disease or Syndrome
Myofibrillar myopathy is characterized by slowly progressive weakness that can involve both proximal and distal muscles. Distal muscle weakness is present in about 80% of individuals and is more pronounced than proximal weakness in about 25%. A minority of individuals experience sensory symptoms, muscle stiffness, aching, or cramps. Peripheral neuropathy is present in about 20% of affected individuals. Overt cardiomyopathy is present in 15%-30%.
Hyperparathyroidism, neonatal severe primary
MedGen UID:
318673
Concept ID:
C1832645
Disease or Syndrome
Neonatal severe hyperparathyroidism usually manifests in the first 6 months of life with severe hypercalcemia, bone demineralization, and failure to thrive. Early diagnosis is critical because untreated NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy. Some infants have milder hyperparathyroidism and a substantially milder clinical presentation and natural history (summary by Egbuna and Brown, 2008).
Paroxysmal extreme pain disorder
MedGen UID:
331565
Concept ID:
C1833661
Disease or Syndrome
Paroxysmal extreme pain disorder, formerly known as familial rectal pain, is characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. Onset is usually in the neonatal period or infancy (Fertleman et al., 2006).
Holoprosencephaly 2
MedGen UID:
322517
Concept ID:
C1834877
Disease or Syndrome
Holoprosencephaly (HPE) is a structural anomaly of the brain in which there is failed or incomplete separation of the forebrain early in gestation. Classic HPE encompasses a continuum of brain malformations including (in order of decreasing severity): alobar, semilobar, lobar, and middle interhemispheric variant (MIHV) type HPE; a septopreoptic type has also been described. Other CNS abnormalities not specific to HPE may also occur. HPE is accompanied by a spectrum of characteristic craniofacial anomalies in approximately 80% of individuals with HPE. Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. Seizures and pituitary dysfunction are common. Most affected fetuses do not survive; severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months. Mildly manifesting individuals without appreciable brain anomalies on conventional neuroimaging may be described as having “microform” HPE.
Visceral myopathy
MedGen UID:
331900
Concept ID:
C1835084
Disease or Syndrome
Familial visceral myopathy is a rare inherited form of myopathic pseudoobstruction, characterized by impaired function of enteric smooth muscle cells resulting in abnormal intestinal mobility, severe abdominal pain, malnutrition, and even death (Lehtonen et al., 2012). Visceral myopathy represents a phenotypic spectrum of disease characterized by inter- and intrafamilial variability, in which the most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and chronic dependence on total parenteral nutrition (TPN) and urinary catheterization (summary by Wangler et al., 2014). Another form of visceral myopathy with functional gastrointestinal obstruction is associated with external ophthalmoplegia (277320). Functional gastrointestinal obstruction also occurs in association with other abnormalities, such as 'prune belly' syndrome (100100) and Barrett esophagus (Mungan syndrome; 611376). Chronic intestinal pseudoobstruction can also be neuropathic in origin (see 609629).
Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease
MedGen UID:
373160
Concept ID:
C1836727
Disease or Syndrome
The neurologic variant of Waardenburg-Shah syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.
Emanuel syndrome
MedGen UID:
323030
Concept ID:
C1836929
Disease or Syndrome
Emanuel syndrome is characterized by severe intellectual disability, microcephaly, failure to thrive, preauricular tags or pits, ear anomalies, cleft or high-arched palate, micrognathia, kidney abnormalities, congenital heart defects, and genital abnormalities in males.
Sacral defect with anterior meningocele
MedGen UID:
325455
Concept ID:
C1838568
Disease or Syndrome
Sacral defect with anterior meningocele (SDAM) is a form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant (Chatkupt et al., 1994). Welch and Aterman (1984) gave a population frequency of 0.14%. Caudal dysgenesis syndrome and caudal regression syndrome are broad terms that refer to a heterogeneous constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. Approximately 15 to 25% of mothers of children with caudal dysgenesis have insulin-dependent diabetes mellitus (222100) (Lynch et al., 2000). See also Currarino syndrome (176450), a similar disorder caused by mutation in the HLXB9 gene (142994) on chromosome 7q36. Currarino syndrome classically comprises the triad of hemisacrum, anorectal malformation, and presacral mass. However, Currarino syndrome also shows phenotypic variability: Lynch et al. (2000) stated that there is variable expressivity of clinical features and that some patients with Currarino syndrome are asymptomatic. Kochling et al. (2001) found the complete triad of Currarino syndrome in only 8 of 23 patients with mutations in the HLXB9 gene, These reports suggest that some patients previously reported as having forms of sacral agenesis, including SDAM, may have had Currarino syndrome and vice versa. See also spina bifida (182940), which can be seen in some patients with sacral agenesis or caudal regression syndrome and may be etiologically related.
Puerto rican infant hypotonia syndrome
MedGen UID:
333148
Concept ID:
C1838651
Disease or Syndrome
Early infantile epileptic encephalopathy 2
MedGen UID:
326463
Concept ID:
C1839333
Disease or Syndrome
EIEE2 is an X-linked dominant severe neurologic disorder characterized by onset of seizures in the first months of life and severe global developmental delay resulting in mental retardation and poor motor control. Other features include lack of speech development, subtle dysmorphic facial features, sleep disturbances, gastrointestinal problems, and stereotypic hand movements. There is some phenotypic overlap with Rett syndrome (312750), but EIEE2 is considered to be a distinct entity (summary by Fehr et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Leiomyomatosis, esophageal and vulval, with nephropathy
MedGen UID:
333429
Concept ID:
C1839884
Disease or Syndrome
Chromosome 1p36 deletion syndrome
MedGen UID:
334629
Concept ID:
C1842870
Disease or Syndrome
1p36 deletion syndrome is characterized by typical craniofacial features consisting of straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, pointed chin, large, late-closing anterior fontanel (77%), microbrachycephaly (65%), epicanthal folds (50%), and posteriorly rotated, low-set, abnormal ears. Other characteristic findings include brachy/camptodactyly and short feet. Developmental delay/intellectual disability of variable degree are present in all, and hypotonia in 95%. Seizures occur in 44%-58% of affected individuals. Other findings include structural brain abnormalities (88%), congenital heart defects (71%), eye/vision problems (52%), hearing loss (47%), skeletal anomalies (41%), abnormalities of the external genitalia (25%), and renal abnormalities (22%).
ATR-X syndrome
MedGen UID:
337145
Concept ID:
C1845055
Disease or Syndrome
Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia. Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Although all affected individuals have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
Creatine deficiency, X-linked
MedGen UID:
337451
Concept ID:
C1845862
Disease or Syndrome
The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CRTR) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; about 40% have movement disorder. Onset is between ages three months and three years. Only 14 individuals with AGAT deficiency have been reported. The phenotype of CRTR deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, movement disorder and behavior disorder; age at diagnosis ranges from two to 66 years. Clinical phenotype of females heterozygous for CRTR deficiency ranges from asymptomatic to severe phenotype resembling male phenotype.
FG syndrome 2
MedGen UID:
337461
Concept ID:
C1845902
Disease or Syndrome
Although the phenotypic spectrum and severity of FG syndrome is wide, the cardinal features include congenital hypotonia, delayed speech development, relative macrocephaly, dysmorphic facies, and anal anomalies or severe constipation (Unger et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450).
MECP2 duplication syndrome
MedGen UID:
337496
Concept ID:
C1846058
Mental or Behavioral Dysfunction
The MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by infantile hypotonia, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals) and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and related clinical findings, often associated with concomitant X-chromosomal abnormalities that prevent inactivation of the duplicated region. Generalized tonic-clonic seizures are most often observed; atonic seizures and absence seizures have also been described. One third of affected males are never able to walk independently. Almost 50% of affected males die before age 25 years, presumably from complications of recurrent infection and/or neurologic deterioration. In addition to the core features, autistic behaviors and gastrointestinal dysfunction have been observed in several affected boys. Although interfamilial phenotypic variability is observed, severity is usually consistent within families.
Thyroid dyshormonogenesis 1
MedGen UID:
336422
Concept ID:
C1848805
Disease or Syndrome
Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). Dyshormonogenesis can be caused by recessive defects at any of the steps required for normal thyroid hormone synthesis. In untreated patients thyroid dyshormonogenesis is typically associated with goitrous enlargement of the thyroid secondary to long-term thyrotropin (TSH; see 188540) stimulation. Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder.
Susceptibility to acute rheumatic fever
MedGen UID:
376575
Concept ID:
C1849384
Finding
Neuroferritinopathy
MedGen UID:
381211
Concept ID:
C1853578
Disease or Syndrome
Neuroferritinopathy typically presents with progressive adult-onset chorea or dystonia affecting one or two limbs, and subtle cognitive deficits. The movement disorder involves additional limbs within five to ten years and becomes more generalized within 20 years. When present, asymmetry remains throughout the course of the disorder. The majority of individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.
Wiedemann-Steiner syndrome
MedGen UID:
340266
Concept ID:
C1854630
Disease or Syndrome
Wiedemann-Steiner syndrome is characterized by hypertrichosis cubiti associated with short stature; consistent facial features, including long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures; mild to moderate intellectual disability; behavioral difficulties; and hypertrichosis on the back (summary by Jones et al., 2012).
Kaufman oculocerebrofacial syndrome
MedGen UID:
343403
Concept ID:
C1855663
Disease or Syndrome
Bartter syndrome antenatal type 2
MedGen UID:
343428
Concept ID:
C1855849
Disease or Syndrome
Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body. In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth. Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness). Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.
Hyperphosphatasia with mental retardation syndrome 1
MedGen UID:
383800
Concept ID:
C1855923
Disease or Syndrome
Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010). Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation Syndrome See also HPMRS2 (614749), caused by mutation in the PIGO gene (614730) on chromosome 9p13; HPMRS3 (614207), caused by mutation in the PGAP2 gene (615187) on chromosome 11p15; HPMRS4 (615716), caused by mutation in the PGAP3 gene (611801) on chromosome 17q12; and HPMRS5 (616025), caused by mutation in the PIGW gene (610275) on chromosome 17q12.
Mowat-Wilson syndrome
MedGen UID:
341067
Concept ID:
C1856113
Disease or Syndrome
Mowat-Wilson syndrome (MWS) is characterized by the following: Distinctive facial features. Structural anomalies including: Hirschsprung disease. Genitourinary anomalies (particularly hypospadias in males). Congenital heart defects (particularly abnormalities of the pulmonary arteries and/or valves). Agenesis or hypogenesis of the corpus callosum. Eye defects (microphthalmia and Axenfeld anomaly). Functional differences including: Moderate to severe intellectual disability. Severe speech impairment with relative preservation of receptive language. Seizures. Growth retardation with microcephaly. Chronic constipation in those without Hirschsprung disease.
Spinal muscular atrophy with respiratory distress 1
MedGen UID:
388083
Concept ID:
C1858517
Disease or Syndrome
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited condition that causes muscle weakness and respiratory failure typically beginning in infancy. Early features of this condition are difficult and noisy breathing, especially when inhaling; a weak cry; problems feeding; and recurrent episodes of pneumonia. Typically between the ages of 6 weeks and 6 months, infants with this condition will experience a sudden inability to breathe due to paralysis of the muscle that separates the abdomen from the chest cavity (the diaphragm). Normally, the diaphragm contracts and moves downward during inhalation to allow the lungs to expand. With diaphragm paralysis, affected individuals require life-long support with a machine to help them breathe (mechanical ventilation). Rarely, children with SMARD1 develop signs or symptoms of the disorder later in childhood. Soon after respiratory failure occurs, individuals with SMARD1 develop muscle weakness in their distal muscles. These are the muscles farther from the center of the body, such as muscles in the hands and feet. The weakness soon spreads to all muscles; however, within 2 years, the muscle weakness typically stops getting worse. Some individuals may retain a low level of muscle function, while others lose all ability to move their muscles. Muscle weakness severely impairs motor development, such as sitting, standing, and walking. Some affected children develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). After approximately the first year of life, individuals with SMARD1 may lose their deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer. Other features of SMARD1 can include reduced pain sensitivity, excessive sweating (hyperhidrosis), loss of bladder and bowel control, and an irregular heartbeat (arrhythmia).
Congenital central hypoventilation
MedGen UID:
347052
Concept ID:
C1859049
Disease or Syndrome
Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory and autonomic regulation. It is typically characterized by a classic presentation in newborns and, rarely, a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as: Apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; Autonomic nervous system dysregulation (ANSD); and In some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed as newborns and ventilated conservatively and consistently throughout childhood have now reached the age of 20 to 30 years; they are highly functional and live independently. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have now reached the age of 30 to 55 years.
Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome
MedGen UID:
347111
Concept ID:
C1859252
Disease or Syndrome
Anal sphincter myopathy, internal
MedGen UID:
349633
Concept ID:
C1862935
Disease or Syndrome
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 4
MedGen UID:
350480
Concept ID:
C1864668
Disease or Syndrome
Progressive external ophthalmoplegia-4 is an autosomal dominant form of mitochondrial disease that variably affects skeletal muscle, the nervous system, the liver, and the gastrointestinal tract. Age at onset ranges from infancy to adulthood. The phenotype ranges from relatively mild, with adult-onset skeletal muscle weakness and weakness of the external eye muscles, to severe, with a multisystem disorder characterized by delayed psychomotor development, lactic acidosis, constipation, and liver involvement (summary by Young et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Ehlers-Danlos syndrome, musculocontractural type
MedGen UID:
356497
Concept ID:
C1866294
Disease or Syndrome
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998). The major characteristics of the musculocontractural form of EDS include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement (summary by Malfait et al., 2010). Genetic Heterogeneity of Musculocontractural Ehlers-Danlos Syndrome Ehlers-Danlos syndrome musculocontractural type 2 (EDSMC2; 615539) is caused by mutation in the DSE gene (605942) on chromosome 6q22.
Bartter syndrome antenatal type 1
MedGen UID:
355727
Concept ID:
C1866495
Disease or Syndrome
Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body. In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth. Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness). Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.
Leukodystrophy, adult-onset, autosomal dominant
MedGen UID:
356995
Concept ID:
C1868512
Disease or Syndrome
Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011).
Gaucher disease, type 1
MedGen UID:
409531
Concept ID:
C1961835
Disease or Syndrome
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
Mental retardation, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Disease or Syndrome
Pitt-Hopkins syndrome
MedGen UID:
370910
Concept ID:
C1970431
Disease or Syndrome
Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial features which become more apparent with age (100%), developmental delay/intellectual disability (100%), and episodic hyperventilation and/or breath-holding while awake (55%-60%). Global developmental delays are significant and intellectual disability is moderate to severe: mean age of walking is four to six years; most affected individuals are nonverbal. Other common findings are behavioral issues, hand stereotypic movements, seizures (40%-50%), constipation, and severe myopia.
Diastasis recti and weakness of the linea alba
MedGen UID:
394255
Concept ID:
C2677303
Disease or Syndrome
Stevenson-Carey syndrome
MedGen UID:
383183
Concept ID:
C2677763
Disease or Syndrome
Tetraamelia with ectodermal dysplasia and lacrimal duct abnormalities
MedGen UID:
413568
Concept ID:
C2749282
Disease or Syndrome
Lipodystrophy, congenital generalized, type 4
MedGen UID:
412871
Concept ID:
C2750069
Disease or Syndrome
Congenital generalized lipodystrophy type 4 combines the phenotype of classic Berardinelli-Seip lipodystrophy (608594) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Spastic paraplegia 44, autosomal recessive
MedGen UID:
413042
Concept ID:
C2750784
Disease or Syndrome
Infantile Parkinsonism-dystonia
MedGen UID:
413468
Concept ID:
C2751067
Disease or Syndrome
Infantile parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities. Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), which represents an increase in dopamine metabolites (review by Kurian et al., 2011). For an overlapping phenotype, see tyrosine hydroxylase deficiency (605407), also known as autosomal recessive Segawa syndrome.
Amyloidogenic transthyretin amyloidosis
MedGen UID:
414031
Concept ID:
C2751492
Disease or Syndrome
Familial transthyretin (TTR) amyloidosis is characterized by a slowly progressive peripheral sensorimotor neuropathy and 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.
Hirschsprung disease 1
MedGen UID:
419188
Concept ID:
C2931876
Disease or Syndrome
Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. The aganglionic segment includes the distal rectum and a variable length of contiguous proximal intestine. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%-20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Rarely, the aganglionosis extends into the small bowel or even more proximally to encompass the entire bowel (total intestinal aganglionosis). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, and may occur as an isolated finding or as part of a multisystem disorder. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed until late childhood or adulthood, HSCR should be considered in anyone with lifelong severe constipation. Individuals with HSCR are at risk for enterocolitis and/or potentially lethal intestinal perforation.
Rett syndrome, congenital variant
MedGen UID:
462055
Concept ID:
C3150705
Disease or Syndrome
The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005).
Chromosome 4q32.1-q32.2 triplication syndrome
MedGen UID:
462207
Concept ID:
C3150857
Disease or Syndrome
Mitochondrial DNA depletion syndrome 4B, MNGIE type
MedGen UID:
462264
Concept ID:
C3150914
Disease or Syndrome
Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).
Proximal tubulopathy, diabetes mellitus and cerebellar ataxia
MedGen UID:
463309
Concept ID:
C3151959
Disease or Syndrome
Parkinson disease, late-onset
MedGen UID:
463618
Concept ID:
C3160718
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME
MedGen UID:
481545
Concept ID:
C3279915
Disease or Syndrome
Pitt-Hopkins-like syndrome 2
MedGen UID:
482109
Concept ID:
C3280479
Disease or Syndrome
Hypothyroidism, congenital, nongoitrous, 6
MedGen UID:
482447
Concept ID:
C3280817
Disease or Syndrome
Congenital order of glycosylation type 1r
MedGen UID:
482714
Concept ID:
C3281084
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Hypothyroidism, congenital, nongoitrous, 1
MedGen UID:
487729
Concept ID:
C3493776
Disease or Syndrome
Resistance to thyroid-stimulating hormone (TSH; see 188540), a hallmark of congenital nongoitrous hypothyroidism, causes increased levels of plasma TSH and low levels of thyroid hormone. Only a subset of patients develop frank hypothyroidism; the remainder are euthyroid and asymptomatic (so-called compensated hypothyroidism) and are usually detected by neonatal screening programs (Paschke and Ludgate, 1997). Genetic Heterogeneity of Congenital Nongoitrous Hypothyroidism CHNG2 (218700) is caused by mutation in the PAX8 gene (167415) on chromosome 2q12-q14; CHNG3 (609893) maps to a locus on chromosome 15q25.3; CHNG4 (275100) is caused by mutation in the TSHB gene (188540) on chromosome 1p13; CHNG5 (225250) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q34; and CHNG6 (614450) is caused by mutation in the THRA gene (190120) on chromosome 17q21.1.
Spastic paraplegia 54, autosomal recessive
MedGen UID:
761341
Concept ID:
C3539495
Disease or Syndrome
Spastic paraplegia-54 is a complicated form of spastic paraplegia, a neurodegenerative disorder affecting fibers of the corticospinal tract. Affected individuals have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak (summary by Schuurs-Hoeijmakers et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Urofacial syndrome 2
MedGen UID:
767434
Concept ID:
C3554520
Disease or Syndrome
Urofacial syndrome (UFS; Ochoa syndrome) is an autosomal recessive disorder characterized by congenital urinary bladder dysfunction associated with an abnormal facial expression upon smiling, laughing, and crying. Affected individuals have an overactive detrusor muscle that fails to fully expel urine because of concomitant internal sphincter contraction, and patients may experience lifelong urinary incontinence, recurrent urosepsis, vesicoureteral reflux, and renal failure. In addition, some patients have severe constipation, indicating a generalized elimination defect (summary by Stuart et al., 2013). For a discussion of genetic heterogeneity of UFS, see UFS1 (236730).
Blepharophimosis-ptosis-intellectual disability syndrome
MedGen UID:
815022
Concept ID:
C3808692
Disease or Syndrome
BPIDS is characterized by blepharophimosis, ptosis, mild upslanting of the palpebral fissures, epicanthus, ectodermal anomalies, developmental delay, and severe intellectual disability with absent speech. Proportionate growth retardation with a small head circumference/microcephaly, congenital malformations, muscular hypotonia, anomalies on brain imaging with hypoplasia of the corpus callosum, and low cholesterol levels are variably present (Basel-Vanagaite et al., 2012).
Infantile neuroaxonal neurodegeneration with facial dysmorphism
MedGen UID:
815784
Concept ID:
C3809454
Disease or Syndrome
Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. Affected individuals show very poor, if any, normal cognitive development. Some patients are never learn to sit or walk independently (summary by Al-Sayed et al., 2013).
Prader-Willi-like syndrome
MedGen UID:
816207
Concept ID:
C3809877
Disease or Syndrome
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE VII
MedGen UID:
816212
Concept ID:
C3809882
Disease or Syndrome

Recent clinical studies

Etiology

López J, Botrán M, García A, González R, Solana MJ, Urbano J, Fernández SN, Sánchez C, López-Herce J
J Pediatr 2015 Oct;167(4):857-861.e1. Epub 2015 Aug 5 doi: 10.1016/j.jpeds.2015.06.046. [Epub ahead of print] PMID: 26254837
Prichard D, Bharucha A
Int J Palliat Nurs 2015 Jun;21(6):272, 274-80. doi: 10.12968/ijpn.2015.21.6.272. PMID: 26126675
Thosani S, Ayala-Ramirez M, Román-González A, Zhou S, Thosani N, Bisanz A, Jimenez C
Eur J Endocrinol 2015 Sep;173(3):377-87. Epub 2015 Jun 9 doi: 10.1530/EJE-15-0456. [Epub ahead of print] PMID: 26060051
Werth BL, Williams KA, Pont LG
Arch Gerontol Geriatr 2015 May-Jun;60(3):418-24. Epub 2015 Feb 16 doi: 10.1016/j.archger.2015.02.004. [Epub ahead of print] PMID: 25736738
van Meegdenburg MM, Heineman E, Broens PM
Am J Surg 2015 Aug;210(2):357-64. Epub 2015 Jan 31 doi: 10.1016/j.amjsurg.2014.09.038. [Epub ahead of print] PMID: 25721649

Diagnosis

Wald A
JAMA 2016 Jan 12;315(2):185-91. doi: 10.1001/jama.2015.16994. PMID: 26757467
Pfeifer J
Rozhl Chir 2015 Sep;94(9):349-61. PMID: 26537099
Gupta S, Patel H, Scopel J, Mody RR
J Opioid Manag 2015 Jul-Aug;11(4):325-38. doi: 10.5055/jom.2015.0282. PMID: 26312960
Thosani S, Ayala-Ramirez M, Román-González A, Zhou S, Thosani N, Bisanz A, Jimenez C
Eur J Endocrinol 2015 Sep;173(3):377-87. Epub 2015 Jun 9 doi: 10.1530/EJE-15-0456. [Epub ahead of print] PMID: 26060051
Kovacic K, Sood MR, Mugie S, Di Lorenzo C, Nurko S, Heinz N, Ponnambalam A, Beesley C, Sanghavi R, Silverman AH
J Pediatr 2015 Jun;166(6):1482-7.e1. doi: 10.1016/j.jpeds.2015.03.016. PMID: 26008173

Therapy

Pfeifer J
Rozhl Chir 2015 Sep;94(9):349-61. PMID: 26537099
López J, Botrán M, García A, González R, Solana MJ, Urbano J, Fernández SN, Sánchez C, López-Herce J
J Pediatr 2015 Oct;167(4):857-861.e1. Epub 2015 Aug 5 doi: 10.1016/j.jpeds.2015.06.046. [Epub ahead of print] PMID: 26254837
Prichard D, Bharucha A
Int J Palliat Nurs 2015 Jun;21(6):272, 274-80. doi: 10.12968/ijpn.2015.21.6.272. PMID: 26126675
Thosani S, Ayala-Ramirez M, Román-González A, Zhou S, Thosani N, Bisanz A, Jimenez C
Eur J Endocrinol 2015 Sep;173(3):377-87. Epub 2015 Jun 9 doi: 10.1530/EJE-15-0456. [Epub ahead of print] PMID: 26060051
Thomas RH, Luthin DR
Pharmacotherapy 2015 Jun;35(6):613-30. Epub 2015 May 27 doi: 10.1002/phar.1594. [Epub ahead of print] PMID: 26016701

Prognosis

Pfeifer J
Rozhl Chir 2015 Sep;94(9):349-61. PMID: 26537099
López J, Botrán M, García A, González R, Solana MJ, Urbano J, Fernández SN, Sánchez C, López-Herce J
J Pediatr 2015 Oct;167(4):857-861.e1. Epub 2015 Aug 5 doi: 10.1016/j.jpeds.2015.06.046. [Epub ahead of print] PMID: 26254837
Graf W, Sonesson AC, Lindberg B, Åkerud P, Karlbom U
Neurogastroenterol Motil 2015 May;27(5):734-9. Epub 2015 Mar 25 doi: 10.1111/nmo.12546. [Epub ahead of print] PMID: 25810166
Heidelbaugh JJ, Stelwagon M, Miller SA, Shea EP, Chey WD
Am J Gastroenterol 2015 Apr;110(4):580-7. Epub 2015 Mar 17 doi: 10.1038/ajg.2015.67. [Epub ahead of print] PMID: 25781368Free PMC Article
Chinzon D, Dias-Bastos TR, Medeiros da Silva A, Eisig JN, Latorre Mdo R
Curr Med Res Opin 2015 Jan;31(1):57-64. Epub 2014 Oct 31 doi: 10.1185/03007995.2014.973485. [Epub ahead of print] PMID: 25295483

Clinical prediction guides

Wald A
JAMA 2016 Jan 12;315(2):185-91. doi: 10.1001/jama.2015.16994. PMID: 26757467
López J, Botrán M, García A, González R, Solana MJ, Urbano J, Fernández SN, Sánchez C, López-Herce J
J Pediatr 2015 Oct;167(4):857-861.e1. Epub 2015 Aug 5 doi: 10.1016/j.jpeds.2015.06.046. [Epub ahead of print] PMID: 26254837
Kovacic K, Sood MR, Mugie S, Di Lorenzo C, Nurko S, Heinz N, Ponnambalam A, Beesley C, Sanghavi R, Silverman AH
J Pediatr 2015 Jun;166(6):1482-7.e1. doi: 10.1016/j.jpeds.2015.03.016. PMID: 26008173
Braunschmid T, Stift A, Mittlböck M, Lord A, Weiser FA, Riss S
Int J Surg 2015 Jul;19:42-5. Epub 2015 May 15 doi: 10.1016/j.ijsu.2015.04.045. [Epub ahead of print] PMID: 25980396
Graf W, Sonesson AC, Lindberg B, Åkerud P, Karlbom U
Neurogastroenterol Motil 2015 May;27(5):734-9. Epub 2015 Mar 25 doi: 10.1111/nmo.12546. [Epub ahead of print] PMID: 25810166

Recent systematic reviews

Patel AS, Saratzis A, Arasaradnam R, Harmston C
Dis Colon Rectum 2015 Oct;58(10):999-1013. doi: 10.1097/DCR.0000000000000428. PMID: 26347973
Maeda Y, O'Connell PR, Lehur PA, Matzel KE, Laurberg S; European SNS Bowel Study Group
Colorectal Dis 2015 Apr;17(4):O74-87. doi: 10.1111/codi.12905. PMID: 25603960
Ding W, Jiang J, Feng X, Ni L, Li J, Li N
Dis Colon Rectum 2015 Jan;58(1):91-6. doi: 10.1097/DCR.0000000000000222. PMID: 25489699
Leonard J, Baker DE
Ann Pharmacother 2015 Mar;49(3):360-5. Epub 2014 Dec 3 doi: 10.1177/1060028014560191. [Epub ahead of print] PMID: 25471070
Camilleri M, Drossman DA, Becker G, Webster LR, Davies AN, Mawe GM
Neurogastroenterol Motil 2014 Oct;26(10):1386-95. Epub 2014 Aug 28 doi: 10.1111/nmo.12417. [Epub ahead of print] PMID: 25164154Free PMC Article

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