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Zellweger syndrome(ZS)

MedGen UID:
21958
Concept ID:
C0043459
Disease or Syndrome
Synonyms: Peroxisome biogenesis disorder 1a; Peroxisome biogenesis disorder 1A (Zellweger); Zellweger leukodystrophy; ZS
Modes of inheritance:
Heterogeneous
MedGen UID:
67020
Concept ID:
C0242960
Organism Attribute
Source: HPO
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Zellweger's syndrome (88469006); Zellweger syndrome (88469006); Cerebrohepatorenal syndrome (88469006)
 
Gene (location): PEX1 (7q21.2)
OMIM®: 214100
Orphanet: ORPHA912

Disease characteristics

Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) is a continuum comprising three phenotypes — Zellweger syndrome (ZS), the most severe; neonatal adrenoleukodystrophy (NALD); and infantile Refsum disease (IRD), the least severe — that were originally described before the biochemical and molecular bases of these disorders had been fully determined. Individuals with PBD, ZSS usually come to clinical attention in the newborn period or later in childhood. In the newborn period, affected children are hypotonic, feed poorly, and have distinctive facies, seizures, and liver cysts with hepatic dysfunction. Bony stippling (chondrodysplasia punctata) of the patella(e) and other long bones may occur. Infants with ZS are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Older children have retinal dystrophy, sensorineural hearing loss, developmental delay with hypotonia, and liver dysfunction. The clinical courses of NALD and IRD are variable and may include developmental delays, hearing loss, vision impairment, liver dysfunction, episodes of hemorrhage, and intracranial bleeding. While some children can be very hypotonic, others learn to walk and talk. The condition is often slowly progressive. [from GeneReviews]
Authors:
Steven J Steinberg  |  Gerald V Raymond  |  Nancy E Braverman, et. al.   view full author information

Additional descriptions

From OMIM
Zellweger syndrome is an autosomal recessive systemic disorder characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life (summary by Wanders, 2004). 'Zellweger syndrome' is the prototype of a large group of peroxisomal disorders, which can be classified into 2 main groups: (1) disorders of peroxisome biogenesis and (2) single peroxisomal enzyme deficiencies (see 264470). The peroxisome biogenesis disorders (PBDs) fall into 4 main phenotypic classes. Three of them, Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), have multiple complementation groups and form a spectrum of overlapping features, with the most severe being the Zellweger syndrome and the least severe infantile Refsum disease. The fourth group, rhizomelic chondrodysplasia punctata (RCDP1; 215100), is a distinct PBD phenotype (summary by Moser et al., 1995, Wanders, 2004). Heimler syndrome, a rare autosomal recessive disorder encompassing sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities, represents a discrete phenotypic entity at the mildest end of the PBD spectrum (Ratbi et al., 2015). Genetic Heterogeneity of Zellweger Syndrome Zellweger syndrome (denoted by the suffix 'A' in the symbol) is a genetically heterogeneous disorder and can be caused by mutation in any one of several genes, known as pexins, involved in peroxisome biogenesis. The pexin (PEX) genes encode proteins essential for the assembly of functional peroxisomes (summary by Distel et al., 1996). Forms of Zellweger syndrome include PBD1A, caused by mutation in the PEX1 gene on chromosome 7q21; PBD2A (214110), caused by mutation in the PEX5 (600414) gene on chromosome 12p13; PBD3A (614859), caused by mutation in the PEX12 (601758) gene on chromosome 17; PBD4A (614862), caused by mutation in the PEX6 (601498) gene on chromosome 6p21; PBD5A (614866), caused by mutation in the PEX2 (170993) gene on chromosome 8q21; PBD6A (614870), caused by mutation in the PEX10 (602859) gene on chromosome 1p36; PBD7A (614872), caused by mutation in the PEX26 (608666) gene on chromosome 22q11; PBD8A (614876), caused by mutation in the PEX16 (603360) gene on chromosome 11p12; PBD10A (614882), caused by mutation in the PEX3 (603164) gene on chromosome 6q23-q24; PBD11A (614883), caused by mutation in the PEX13 (601789) gene on chromosome 2p15; PBD12A (614886), caused by mutation in the PEX19 (600279) gene on chromosome 1q22; and PBD13A (614887), caused by mutation in the PEX14 gene (601791) on chromosome 1p36.2. Mutation in the pexin genes also causes the less severe phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD); see PBD1B (601539) for a phenotypic description and discussion of genetic heterogeneity of these PBDs. Heimler syndrome-1 (HMLR1; 234580) and -2 (HMLR2; 616617) are caused by mutation in the PEX1 and PEX6 genes, respectively. The rhizomelic chondrodysplasia subtype of PBD (RCDP1, PBD9; 215100), and a PBD without rhizomelia (PBD9B; 614879), are caused by mutation in the PEX7 gene (601757) on chromosome 6q22-q24. In addition to the defects in peroxisome assembly, Distel et al. (1996) noted that peroxisomal disorders include a number of single peroxisomal enzyme deficiencies: X-linked adrenoleukodystrophy (ALD; 300100), acyl-coenzyme A oxidase deficiency (264470), DHAPAT deficiency (222765), alkyl-DHAP synthase deficiency (600121), glutaric aciduria type III (231690), classic Refsum disease (266500), hyperoxaluria type I (259900), and acatalasia (115500). A peroxisomal and mitochondrial fission defect results in a lethal encephalopathy (EMPF; 614388).  http://www.omim.org/entry/214100
From GHR
Zellweger spectrum disorder is a group of conditions that have overlapping signs and symptoms and affect many parts of the body. This group of conditions includes Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease. These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. Zellweger syndrome is the most severe form of the Zellweger spectrum disorder, NALD is intermediate in severity, and infantile Refsum disease is the least severe form. Because these three conditions are now considered one disorder, some researchers prefer not to use the separate condition names but to instead refer to cases as severe, intermediate, or mild.Individuals with Zellweger syndrome, at the severe end of the spectrum, develop signs and symptoms of the condition during the newborn period. These infants experience weak muscle tone (hypotonia), feeding problems, hearing and vision loss, and seizures. These problems are caused by the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter. Destruction of myelin (demyelination) leads to loss of white matter (leukodystrophy). Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanels) and characteristic bone spots known as chondrodysplasia punctata that can be seen on x-ray. Affected individuals have distinctive facial features, including a flattened face, broad nasal bridge, and high forehead. Children with Zellweger syndrome typically do not survive beyond the first year of life.People with NALD or infantile Refsum disease, which are at the less-severe end of the spectrum, have more variable features than those with Zellweger syndrome and usually do not develop signs and symptoms of the disease until late infancy or early childhood. They may have many of the features of Zellweger syndrome; however, their condition typically progresses more slowly. Children with these less-severe conditions often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Most people with NALD survive into childhood, and those with infantile Refsum disease may reach adulthood. In rare cases, individuals at the mildest end of the condition spectrum have developmental delay in childhood and hearing loss or vision problems beginning in adulthood and do not develop the other features of this disorder.  https://ghr.nlm.nih.gov/condition/zellweger-spectrum-disorder

Clinical features

Small adrenal gland
MedGen UID:
83342
Concept ID:
C0342491
Finding
Developmental hypoplasia of the adrenal glands.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Retinitis pigmentosa
MedGen UID:
20551
Concept ID:
C0035334
Disease or Syndrome
Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited ocular diseases that result in a progressive retinal degeneration affecting 1 in 3,000 to 5,000 people (Veltel et al., 2008). Symptoms include night blindness, the development of tunnel vision, and slowly progressive decreased central vision starting at approximately 20 years of age. Upon examination, patients have decreased visual acuity, constricted visual fields, dyschromatopsia (tritanopic; see 190900), and the classic fundus appearance with dark pigmentary clumps in the midperiphery and perivenous areas ('bone spicules'), attenuated retinal vessels, cystoid macular edema, fine pigmented vitreous cells, and waxy optic disc pallor. RP is associated with posterior subcapsular cataracts in 39 to 72% of patients, high myopia, astigmatism, keratoconus, and mild hearing loss in 30% of patients (excluding patients with Usher syndrome; see 276900). Fifty percent of female carriers of X-linked RP have a golden reflex in the posterior pole (summary by Kaiser et al., 2004). Juvenile Retinitis Pigmentosa Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (see 204000), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Autosomal recessive forms of juvenile retinitis pigmentosa can be caused by mutation in the SPATA7 (609868), LRAT (604863), and TULP1 (602280) genes (see LCA3, 604232, LCA14, 613341, and LCA15, 613843, respectively). An autosomal dominant form of juvenile retinitis pigmentosa (see 604393) is caused by mutation in the AIPL1 gene (604392).
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Acquired Abnormality
A cataract is a clouding of the lens in your eye. It affects your vision. Cataracts are very common in older people. By age 80, more than half of all Americans either have a cataract or have had cataract surgery. A cataract can occur in either or both eyes. It cannot spread from one eye to the other. Common symptoms are. -Blurry vision. -Colors that seem faded. -Glare - headlights, lamps or sunlight may seem too bright. You may also see a halo around lights. -Not being able to see well at night. -Double vision . -Frequent prescription changes in your eye wear . Cataracts usually develop slowly. New glasses, brighter lighting, anti-glare sunglasses or magnifying lenses can help at first. Surgery is also an option. It involves removing the cloudy lens and replacing it with an artificial lens. Wearing sunglasses and a hat with a brim to block ultraviolet sunlight may help to delay cataracts. NIH: National Eye Institute.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disk (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Brushfield spots
MedGen UID:
266270
Concept ID:
C1303007
Finding
The presence of whitish spots in a ring-like arrangement at the periphery of the iris.
Abnormal electroretinogram
MedGen UID:
341512
Concept ID:
C1849688
Finding
Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.
Opacification of the corneal stroma
MedGen UID:
347281
Concept ID:
C1856661
Finding
Reduced transparency of the stroma of cornea.
Albuminuria
MedGen UID:
1394
Concept ID:
C0001925
Finding
Increased concentration of albumin in the urine.
Cryptorchidism, unilateral or bilateral
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Hypospadias
MedGen UID:
305577
Concept ID:
C1691215
Congenital Abnormality
Location of the urethral opening on the inferior aspect of the penis.
Renal cortical microcysts
MedGen UID:
356391
Concept ID:
C1865877
Finding
Cysts of microscopic size confined to the cortex of the kidney.
Abnormal urinary amino-acid findings
MedGen UID:
892939
Concept ID:
C4020843
Finding
An increased concentration of an amino acid in the urine.
Talipes equinovarus
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Cubitus valgus
MedGen UID:
490152
Concept ID:
C0158465
Acquired Abnormality
Abnormal positioning in which the elbows are turned out.
Toeing-in
MedGen UID:
534039
Concept ID:
C0231791
Finding
The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.
Vertical talus, congenital
MedGen UID:
66821
Concept ID:
C0240912
Congenital Abnormality
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Ulnar deviation of the hand or of fingers of the hand
MedGen UID:
66031
Concept ID:
C0241521
Finding
Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Anatomical Abnormality
Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Enlargement of the liver.
Intrahepatic biliary dysgenesis
MedGen UID:
347107
Concept ID:
C1859235
Finding
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Abnormality of the helix
MedGen UID:
344782
Concept ID:
C1856660
Finding
An abnormality of the helix. The helix is the outer rim of the ear that extends from the insertion of the ear on the scalp (root) to the termination of the cartilage at the earlobe.
Heterotopia
MedGen UID:
40280
Concept ID:
C0008519
Pathologic Function
A mass of histologically normal tissue present in an abnormal location.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
A congenital abnormality of the cerebral hemisphere characterized by an excessive number of small gyri (convolutions) on the surface of the brain.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Sign or Symptom
Reduction of neurologic reflexes such as the knee-jerk reaction.
Subependymal cysts
MedGen UID:
318876
Concept ID:
C1833431
Finding
Cerebral cysts, usually located in the wall of the caudate nucleus or in the caudothalamic groove. They are found in up to 5.2% of all neonates, using transfontanellar ultrasound in the first days of life.
Intellectual disability, progressive
MedGen UID:
337397
Concept ID:
C1846149
Finding
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Hypoplastic olfactory lobes
MedGen UID:
395206
Concept ID:
C1859231
Finding
Aplasia/Hypoplasia of the corpus callosum
MedGen UID:
354608
Concept ID:
C1861866
Finding
Absence or underdevelopment of the corpus callosum.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Albuminuria
MedGen UID:
1394
Concept ID:
C0001925
Finding
Increased concentration of albumin in the urine.
Cryptorchidism, unilateral or bilateral
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Hypospadias
MedGen UID:
305577
Concept ID:
C1691215
Congenital Abnormality
Location of the urethral opening on the inferior aspect of the penis.
Renal cortical microcysts
MedGen UID:
356391
Concept ID:
C1865877
Finding
Cysts of microscopic size confined to the cortex of the kidney.
Abnormal urinary amino-acid findings
MedGen UID:
892939
Concept ID:
C4020843
Finding
An increased concentration of an amino acid in the urine.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Albuminuria
MedGen UID:
1394
Concept ID:
C0001925
Finding
Increased concentration of albumin in the urine.
Elevated long chain fatty acids
MedGen UID:
395207
Concept ID:
C1859241
Finding
Increased concentration of long-chain fatty acid.
Abnormal urinary amino-acid findings
MedGen UID:
892939
Concept ID:
C4020843
Finding
An increased concentration of an amino acid in the urine.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Cubitus valgus
MedGen UID:
490152
Concept ID:
C0158465
Acquired Abnormality
Abnormal positioning in which the elbows are turned out.
Toeing-in
MedGen UID:
534039
Concept ID:
C0231791
Finding
The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.
Vertical talus, congenital
MedGen UID:
66821
Concept ID:
C0240912
Congenital Abnormality
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Widely patent fontanelles and sutures
MedGen UID:
336570
Concept ID:
C1849300
Finding
An abnormally increased width of the cranial fontanelles and sutures.
Brachyturricephaly
MedGen UID:
387833
Concept ID:
C1857484
Finding
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Epiphyseal stippling
MedGen UID:
349104
Concept ID:
C1859126
Finding
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses (FMA:24012).
Bell-shaped thorax
MedGen UID:
351320
Concept ID:
C1865186
Finding
The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, follwed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Protruding tongue
MedGen UID:
66831
Concept ID:
C0241442
Finding
Tongue extending beyond the alveolar ridges or teeth at rest.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Redundant neck skin
MedGen UID:
374440
Concept ID:
C1840319
Finding
Excess skin around the neck, often lying in horizontal folds.
Widely patent fontanelles and sutures
MedGen UID:
336570
Concept ID:
C1849300
Finding
An abnormally increased width of the cranial fontanelles and sutures.
Flat face
MedGen UID:
336577
Concept ID:
C1849339
Absence of concavity or convexity of the face when viewed in profile.
Round face
MedGen UID:
341560
Concept ID:
C1856468
Finding
The facial appearance is more circular than usual as viewed from the front.
Brachyturricephaly
MedGen UID:
387833
Concept ID:
C1857484
Finding
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Redundant neck skin
MedGen UID:
374440
Concept ID:
C1840319
Finding
Excess skin around the neck, often lying in horizontal folds.
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Breech presentation
MedGen UID:
654
Concept ID:
C0006157
Pathologic Function
A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first.

Term Hierarchy

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

Recent clinical studies

Etiology

Lertsirivorakul J, Wongswadiwat M, Treesuwan P
Spec Care Dentist 2014 Jan-Feb;34(1):46-50. Epub 2012 Dec 12 doi: 10.1111/scd.12003. PMID: 24382371
Fedick A, Jalas C, Treff NR
Clin Genet 2014 Apr;85(4):343-6. Epub 2013 May 3 doi: 10.1111/cge.12170. PMID: 23590336
Sun Y, Wang L, Wei X, Zhu Q, Yang Y, Lan Z, Qu N, Chu Y, Wang Y, Yang S, Liang Y, Wang W, Yi X
Clin Chim Acta 2013 Feb 18;417:57-61. Epub 2012 Dec 13 doi: 10.1016/j.cca.2012.12.005. PMID: 23247051
Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE
BMC Med Genet 2012 Aug 15;13:72. doi: 10.1186/1471-2350-13-72. PMID: 22894767Free PMC Article
Dursun A, Gucer S, Ebberink MS, Yigit S, Wanders RJ, Waterham HR
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S345-8. Epub 2009 Dec 23 doi: 10.1007/s10545-009-9010-0. PMID: 20033294

Diagnosis

Komatsuzaki S, Ogawa E, Shimozawa N, Sakamoto O, Haginoya K, Uematsu M, Hasegawa Y, Matsubara Y, Ohura T
Pediatr Int 2015 Dec;57(6):1189-92. Epub 2015 Dec 2 doi: 10.1111/ped.12713. PMID: 26627464
Najafi Sani M, Ahmadi M, Roohani P, Rezaei N
Acta Med Iran 2015 Oct;53(10):656-8. PMID: 26615381
Rosewich H, Waterham H, Poll-The BT, Ohlenbusch A, Gärtner J
Eur J Hum Genet 2015 Aug;23(8) Epub 2014 Nov 19 doi: 10.1038/ejhg.2014.250. PMID: 25407003Free PMC Article
Salpietro V, Phadke R, Saggar A, Hargreaves IP, Yates R, Fokoloros C, Mankad K, Hertecant J, Ruggieri M, McCormick D, Kinali M
Eur J Pediatr 2015 Apr;174(4):557-63. Epub 2014 Oct 7 doi: 10.1007/s00431-014-2431-2. PMID: 25287621
Aydemir O, Kavurt S, Esin S, Kandemir O, Bas AY, Demirel N
J Obstet Gynaecol Res 2014 Jun;40(6):1799-802. doi: 10.1111/jog.12379. PMID: 24888952

Therapy

Colburn JD, Skelo AS, Donahue SP
J AAPOS 2009 Jun;13(3):289-91. doi: 10.1016/j.jaapos.2009.03.004. PMID: 19541270
Arai Y, Kitamura Y, Hayashi M, Oshida K, Shimizu T, Yamashiro Y
Congenit Anom (Kyoto) 2008 Dec;48(4):180-2. doi: 10.1111/j.1741-4520.2008.00201.x. PMID: 18983586
Tanaka K, Shimizu T, Ohtsuka Y, Yamashiro Y, Oshida K
Brain Dev 2007 Oct;29(9):586-9. Epub 2007 Apr 5 doi: 10.1016/j.braindev.2007.02.005. PMID: 17418516
Kawada Y, Khan M, Sharma AK, Ratnayake DB, Dobashi K, Asayama K, Moser HW, Contreras MA, Singh I
Mol Genet Metab 2004 Dec;83(4):297-305. doi: 10.1016/j.ymgme.2004.07.012. PMID: 15589116
Muth A, Mosandl A, Wanders RJ, Nowaczyk MJ, Baric I, Böhles H, Sewell AC
J Inherit Metab Dis 2003;26(6):583-92. PMID: 14605504

Prognosis

Komatsuzaki S, Ogawa E, Shimozawa N, Sakamoto O, Haginoya K, Uematsu M, Hasegawa Y, Matsubara Y, Ohura T
Pediatr Int 2015 Dec;57(6):1189-92. Epub 2015 Dec 2 doi: 10.1111/ped.12713. PMID: 26627464
Malinescu B, Martius E, Pelin AM
Forensic Sci Int 2015 Oct;255:89-95. Epub 2015 Jul 13 doi: 10.1016/j.forsciint.2015.07.009. PMID: 26235911
Lee PR, Raymond GV
Neurology 2013 May 14;80(20):e207-10. doi: 10.1212/WNL.0b013e3182929f8e. PMID: 23671347Free PMC Article
Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE
BMC Med Genet 2012 Aug 15;13:72. doi: 10.1186/1471-2350-13-72. PMID: 22894767Free PMC Article
Dursun A, Gucer S, Ebberink MS, Yigit S, Wanders RJ, Waterham HR
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S345-8. Epub 2009 Dec 23 doi: 10.1007/s10545-009-9010-0. PMID: 20033294

Clinical prediction guides

Abe Y, Honsho M, Nakanishi H, Taguchi R, Fujiki Y
Biochim Biophys Acta 2014 Apr 4;1841(4):610-9. Epub 2014 Jan 10 doi: 10.1016/j.bbalip.2014.01.001. PMID: 24418004
Levesque S, Morin C, Guay SP, Villeneuve J, Marquis P, Yik WY, Jiralerspong S, Bouchard L, Steinberg S, Hacia JG, Dewar K, Braverman NE
BMC Med Genet 2012 Aug 15;13:72. doi: 10.1186/1471-2350-13-72. PMID: 22894767Free PMC Article
Yik WY, Steinberg SJ, Moser AB, Moser HW, Hacia JG
Hum Mutat 2009 Mar;30(3):E467-80. doi: 10.1002/humu.20932. PMID: 19105186Free PMC Article
Breitling R
BMC Pediatr 2004 Mar 12;4:5. doi: 10.1186/1471-2431-4-5. PMID: 15102341Free PMC Article
Muth A, Mosandl A, Wanders RJ, Nowaczyk MJ, Baric I, Böhles H, Sewell AC
J Inherit Metab Dis 2003;26(6):583-92. PMID: 14605504

Recent systematic reviews

Vogel BH, Bradley SE, Adams DJ, D'Aco K, Erbe RW, Fong C, Iglesias A, Kronn D, Levy P, Morrissey M, Orsini J, Parton P, Pellegrino J, Saavedra-Matiz CA, Shur N, Wasserstein M, Raymond GV, Caggana M
Mol Genet Metab 2015 Apr;114(4):599-603. Epub 2015 Feb 12 doi: 10.1016/j.ymgme.2015.02.002. PMID: 25724074
Weller S, Rosewich H, Gärtner J
J Inherit Metab Dis 2008 Apr;31(2):270-80. Epub 2008 Apr 14 doi: 10.1007/s10545-008-0856-3. PMID: 18415699
Kingsley PB, Shah TC, Woldenberg R
NMR Biomed 2006 Jun;19(4):435-62. doi: 10.1002/nbm.1039. PMID: 16763970

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