Format

Send to:

Choose Destination

Links from PubMed

Dandy-Walker syndrome(DWS)

MedGen UID:
4150
Concept ID:
C0010964
Disease or Syndrome
Synonyms: Dandy-walker anomaly; Dandy-Walker cyst; Dandy-Walker malformation; DWS; DWS-Related Dandy Walker Syndrome
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)
Multifactorial inheritance
MedGen UID:
109109
Concept ID:
C0600599
Genetic Function
Sources: HPO, Orphanet
A mode of inheritance that depends on a mixture of major and minor genetic determinants possibly together with environmental factors. Diseases inherited in this manner are termed complex diseases.
Sporadic
MedGen UID:
342827
Concept ID:
C1853237
Finding
Sources: HPO, OMIM
Cases of the disease in question occur without a previous family history, i.e., as isolated cases without being transmitted from a parent and without other siblings being affected.
Sporadic (HPO, OMIM)
SNOMED CT: Dandy-Walker malformation (14447001); Dandy-Walker syndrome (14447001); Dandy-Walker deformity (14447001)
 
Cytogenetic location: 3q22-q24
OMIM®: 220200
HPO: HP:0001305
Orphanet: ORPHA217

Definition

Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985). [from OMIM]

Additional description

From GHR
Dandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions.In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition.Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms.Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features.In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition.Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation.  https://ghr.nlm.nih.gov/condition/dandy-walker-malformation

Clinical features

Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Truncal ataxia
MedGen UID:
96535
Concept ID:
C0427190
Sign or Symptom
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
Joubert syndrome
MedGen UID:
98464
Concept ID:
C0431399
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Thinning and bulging of the posterior fossa bones
MedGen UID:
867417
Concept ID:
C4021788
Finding
Partial absence of cerebellar vermis
MedGen UID:
871190
Concept ID:
C4025667
Congenital Abnormality
Congenital absence of a part of the vermis of cerebellum.
Posterior fossa cyst at the fourth ventricle
MedGen UID:
871328
Concept ID:
C4025816
Finding
Elevated imprint of the transverse sinuses
MedGen UID:
871329
Concept ID:
C4025817
Finding

Term Hierarchy

Conditions with this feature

Beckwith-Wiedemann syndrome
MedGen UID:
2562
Concept ID:
C0004903
Disease or Syndrome
Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.
Chondroectodermal dysplasia
MedGen UID:
8584
Concept ID:
C0013903
Disease or Syndrome
Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals (summary by Ruiz-Perez et al., 2000). The clinical features of the Ellis-van Creveld syndrome appear to be identical regardless of whether the disorder is caused by mutation in the EVC gene (604831) or in the EVC2 gene (607261) (Ruiz-Perez et al., 2003, Galdzicka et al., 2002).
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.
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.
Aase Smith syndrome
MedGen UID:
66316
Concept ID:
C0220686
Disease or Syndrome
A very rare genetic disorder with characteristics of the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate and severe joint contractures. Less than 20 cases have been reported in the literature. The fingers are thin with absent knuckles and reduced creases over the joints and patients show an inability to make a full fist. Additional findings may include deformed ears, ptosis, an inability to open the mouth fully, heart defects, and clubfoot. There are currently no human genes associated with this disease.
Fryns syndrome
MedGen UID:
65088
Concept ID:
C0220730
Disease or Syndrome
Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia or agenesis); characteristic facial appearance (coarse facies, ocular hypertelorism, broad and flat nasal bridge, thick nasal tip, long philtrum, low-set and poorly formed ears, tented upper lip, macrostomia, micrognathia); distal digital hypoplasia (nails, terminal phalanges); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia/renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, genitalia). Survival beyond the neonatal period has been rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common.
Neu-Laxova syndrome
MedGen UID:
78537
Concept ID:
C0265218
Disease or Syndrome
Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (summary by Manning et al., 2004). Genetic Heterogeneity of Neu-Laxova Syndrome NLS2 (616038) is caused by mutation in the PSAT1 gene (610936) on chromosome 9q21.
Walker-Warburg congenital muscular dystrophy
MedGen UID:
75553
Concept ID:
C0265221
Disease or Syndrome
Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. Muscle weakness may improve, worsen, or stabilize in the short term; however, with time progressive weakness and joint contractures, spinal deformities, and respiratory compromise may affect quality of life and life span. The main CMD subtypes, grouped by involved protein function and gene in which causative allelic variants occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutation of POMT1, POMT2, FKTN, FKRP, LARGE1, POMGNT1, and ISPD), SELENON (SEPN1)-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). Several less known CMD subtypes have been reported in a limited number of individuals. Cognitive impairment ranging from intellectual disability to mild cognitive delay, structural brain and/or eye abnormalities, and seizures are found almost exclusively in the dystroglycanopathies while white matter abnormalities without major cognitive involvement tend to be seen in the laminin alpha-2-deficient subtype.
Coffin-Siris syndrome
MedGen UID:
75565
Concept ID:
C0265338
Disease or Syndrome
Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014). Mutations in the ARID1B gene are the most common cause of Coffin-Siris syndrome (Wieczorek et al., 2013). Genetic Heterogeneity of Coffin-Siris Syndrome Forms of Coffin-Siris syndrome have been shown to be caused by mutations in genes encoding subunits of the SWI/SNF complex, also known as the BAF complex, which functions as a chromatin remodeling factor. These include CSS2 (614607), caused by mutation in the ARID1A gene (603024); CSS3 (614608), caused by mutation in the SMARCB1 gene (601607); CSS4 (614609), caused by mutation in the SMARCA4 gene (603254); CSS5 (616938), caused by mutation in the SMARCE1 gene (603111); and CSS6 (617808), caused by mutation in the ARID2 gene (609539). A similar phenotype, Nicolaides-Baraitser syndrome (NCBRS; 601358), is also caused by mutation in a subunit of this complex, i.e., SMARCA2 (600014).
Cutis laxa with osteodystrophy
MedGen UID:
82795
Concept ID:
C0268355
Disease or Syndrome
ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), spans a phenotypic spectrum that includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end. Affected individuals have furrowing of the skin of the whole body that improves with time. They may have other evidence of a generalized connective disorder, including enlarged anterior fontanelle in infancy, congenital dislocation of the hips, inguinal hernias, and high myopia. In most (not all) affected individuals, cortical and cerebellar malformations are present and are associated with severe developmental delays, seizures, and neurologic regression.
Cross syndrome
MedGen UID:
82811
Concept ID:
C0268496
Disease or Syndrome
Chondrodysplasia punctata 2 X-linked dominant
MedGen UID:
79381
Concept ID:
C0282102
Disease or Syndrome
The findings in X-linked chondrodysplasia punctata 2 (CDPX2) range from fetal demise with multiple malformations and severe growth retardation to much milder manifestations, including adults with no recognizable physical abnormalities. At least 95% of liveborn individuals with CDPX2 are female with the following findings: Growth deficiency/short stature. Distinctive craniofacial appearance. Skeletal changes: stippling (chondrodysplasia punctate) on x-rays of the epiphyses of the long bones and vertebrae, the trachea and distal ends of the ribs seen in children prior to completion of normal epiphyseal ossification; rhizomelic (i.e., proximal) shortening of limbs that is often asymmetric; scoliosis. Ectodermal changes: linear or blotchy scaling ichthyosis in the newborn that usually resolves in the first months of life leaving linear or whorled atrophic patches involving hair follicles (follicular atrophoderma); coarse hair with scarring alopecia; occasional flattened or split nails; normal teeth. Ocular changes: cataracts; microphthalmia and/or microcornea. Intellect is usually normal. Rarely affected males have been identified with a phenotype that includes: hypotonia; moderate to profound developmental delay; seizures; cerebellar (primarily vermis) hypoplasia and/or Dandy-Walker variant; and agenesis of the corpus callosum.
Encephalocraniocutaneous lipomatosis
MedGen UID:
140807
Concept ID:
C0406612
Congenital Abnormality
Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007). The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).
Marden-Walker syndrome
MedGen UID:
163206
Concept ID:
C0796033
Disease or Syndrome
A constellation of immobile facies, blepharophimosis, micrognathia, microcephaly, midfacial hypoplasia, multiple contractures, hypotonia, arachnodactyly, developmental delay, and other anomalies.
Oculocerebrocutaneous syndrome
MedGen UID:
163214
Concept ID:
C0796092
Disease or Syndrome
Orbital cysts and other eye defects, multiple cerebral anomalies, and focal dermal defects are the principal characteristics of this syndrome.
Dandy-Walker like malformation with atrioventricular septal defect
MedGen UID:
163220
Concept ID:
C0796137
Disease or Syndrome
The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay (summary by Leonardi et al., 2001; Seidahmed et al., 2011). Genetic Heterogeneity of Ritscher-Schinzel Syndrome See also RTSC2 (300963), caused by mutation in the CCDC22 gene (300859) on chromosome Xp11.
C-like syndrome
MedGen UID:
208678
Concept ID:
C0796232
Disease or Syndrome
Bohring-Opitz syndrome (BOS) is characterized by distinctive facial features and posture, growth failure, variable but usually severe intellectual disability, and variable anomalies. The facial features may include microcephaly or trigonocephaly / prominent (but not fused) metopic ridge, hypotonic facies with full cheeks, synophrys, glabellar and eyelid nevus flammeus (simplex), prominent globes, widely set eyes, palate anomalies, and micrognathia. The BOS posture, which is most striking in early childhood and often becomes less apparent with age, is characterized by flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints. Feeding difficulties in early childhood, including cyclic vomiting, have a significant impact on overall health; feeding tends to improve with age. Seizures are common and typically responsive to standard epileptic medications. Minor cardiac anomalies and transient bradycardia and apnea may be present. Affected individuals may experience recurrent infections, which also tend to improve with age. Isolated case reports suggest that individuals with BOS are at greater risk for Wilms tumor than the general population, but large-scale epidemiologic studies have not been conducted.
Jung Wolff Back Stahl syndrome
MedGen UID:
316973
Concept ID:
C1832362
Disease or Syndrome
Hydrocephalus, autosomal dominant
MedGen UID:
325006
Concept ID:
C1838347
Disease or Syndrome
Congenital disorder of glycosylation type 2D
MedGen UID:
339615
Concept ID:
C1846816
Disease or Syndrome
Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem disorders that are commonly associated with severe psychomotor and mental retardation. The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans (summary by Hansske et al., 2002). For a general discussion of CDGs, see CDG1A (212065).
PHACE syndrome
MedGen UID:
376231
Concept ID:
C1847874
Disease or Syndrome
PHACE is an acronym for a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, hemangiomas of the face (large or complex), arterial anomalies, cardiac anomalies, and eye abnormalities. The association is referred to as PHACES when ventral developmental defects, such as sternal clefting or supraumbilical raphe, are present (summary by Bracken et al., 2011).
Mosaic variegated aneuploidy syndrome
MedGen UID:
338026
Concept ID:
C1850343
Disease or Syndrome
Mosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes, a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism. Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.In MVA syndrome, growth before birth is slow (intrauterine growth restriction). After birth, affected individuals continue to grow at a slow rate and are shorter than average. In addition, they typically have an unusually small head size (microcephaly). Another common feature of MVA syndrome is an increased risk of developing cancer in childhood. Cancers that occur most frequently in affected individuals include a cancer of muscle tissue called rhabdomyosarcoma, a form of kidney cancer known as Wilms tumor, and a cancer of the blood-forming tissue known as leukemia.Less commonly, people with MVA syndrome have eye abnormalities or distinctive facial features, such as a broad nasal bridge and low-set ears. Some affected individuals have brain abnormalities, the most common of which is called Dandy-Walker malformation. Intellectual disability, seizures, and other health problems can also occur in people with MVA syndrome.There are at least three types of MVA syndrome, each with a different genetic cause. Type 1 is the most common and displays the classic signs and symptoms described above. Type 2 appears to have slightly different signs and symptoms than type 1, although the small number of affected individuals makes it difficult to define its characteristic features. Individuals with MVA syndrome type 2 grow slowly before and after birth; however, their head size is typically normal. Some people with MVA syndrome type 2 have unusually short arms. Individuals with MVA syndrome type 2 do not seem to have an increased risk of cancer. Another form of MVA syndrome is characterized by a high risk of developing Wilms tumor. Individuals with this form may also have other signs and symptoms typical of MVA syndrome type 1.
Hydrolethalus syndrome 1
MedGen UID:
343455
Concept ID:
C1856016
Disease or Syndrome
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome
MedGen UID:
384026
Concept ID:
C1856972
Disease or Syndrome
The proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a rare autosomal recessive prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation (summary by Meyer et al., 2010).
Dandy-Walker malformation with postaxial polydactyly
MedGen UID:
341751
Concept ID:
C1857351
Disease or Syndrome
A syndromic disorder with the association between Dandy-Walker malformation and postaxial polydactyly as a major feature. The Dandy-Walker malformation has a variable expression and characteristics of a posterior fossa cyst communicating with the fourth ventricle, the partial or complete absence of the cerebellar vermis, and facultative hydrocephalus. Postaxial polydactyly includes tetramelic postaxial polydactyly of hands and feet with possible enlargement of the fifth metacarpal and metatarsal bones, as well as bifid fifth metacarpals.
Dandy-Walker malformation with mental retardation, macrocephaly, myopia and brachytelephalangy
MedGen UID:
341752
Concept ID:
C1857352
Disease or Syndrome
Plasminogen deficiency, type I
MedGen UID:
369859
Concept ID:
C1968804
Disease or Syndrome
Congenital plasminogen deficiency is a rare autosomal recessive disorder characterized clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. A slightly increased female:male ratio has been observed (1.4:1 to 2:1) (Schuster and Seregard, 2003; Tefs et al., 2006). Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas type II plasminogen deficiency, also known as 'dysplasminogenemia,' is characterized by decreased plasminogen activity with normal or slightly reduced antigen levels. Patients with type II deficiency are usually asymptomatic. Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency. Presumably, normal amounts of plasminogen antigen with decreased activity, as seen in type II, is sufficient for normal wound healing (Schuster and Seregard, 2003).
Meckel syndrome type 4
MedGen UID:
410003
Concept ID:
C1970161
Disease or Syndrome
Meckel syndrome is an autosomal recessive pre- or perinatal lethal disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Baala et al., 2007). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Meckel syndrome type 7
MedGen UID:
382217
Concept ID:
C2673885
Disease or Syndrome
This autosomal recessive disorder is designated Meckel syndrome type 7 based on the classic phenotypic triad of (1) cystic renal disease; (2) a central nervous system abnormality, and (3) hepatic abnormalities, as defined by Meckel (1822), Salonen (1984), and Logan et al. (2011). According to these criteria, polydactyly is a variable feature. Herriot et al. (1991) and Al-Gazali et al. (1996) concluded that Dandy-Walker malformation can be the phenotypic manifestation of a central nervous system malformation in MKS. For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Dandy-walker malformation with occipital cephalocele, autosomal dominant
MedGen UID:
393273
Concept ID:
C2674987
Disease or Syndrome
Chromosome 6pter-p24 deletion syndrome
MedGen UID:
393396
Concept ID:
C2675486
Disease or Syndrome
Growth retardation, developmental delay, coarse facies, and early death
MedGen UID:
414158
Concept ID:
C2752001
Congenital Abnormality
Growth retardation, developmental delay, and facial dysmorphism (GDFD) is an autosomal recessive multiple congenital anomaly syndrome characterized by severe psychomotor retardation, poor overall growth, and dysmorphic facial features. Additional features may include cardiac malformations and deafness (summary by Daoud et al., 2016).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A5
MedGen UID:
461763
Concept ID:
C3150413
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Beltran-Valero de Bernabe et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Joubert syndrome 14
MedGen UID:
482396
Concept ID:
C3280766
Disease or Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Mental retardation, autosomal dominant 12
MedGen UID:
482831
Concept ID:
C3281201
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A7
MedGen UID:
766244
Concept ID:
C3553330
Disease or Syndrome
Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. Muscle weakness may improve, worsen, or stabilize in the short term; however, with time progressive weakness and joint contractures, spinal deformities, and respiratory compromise may affect quality of life and life span. The main CMD subtypes, grouped by involved protein function and gene in which causative allelic variants occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutation of POMT1, POMT2, FKTN, FKRP, LARGE1, POMGNT1, and ISPD), SELENON (SEPN1)-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). Several less known CMD subtypes have been reported in a limited number of individuals. Cognitive impairment ranging from intellectual disability to mild cognitive delay, structural brain and/or eye abnormalities, and seizures are found almost exclusively in the dystroglycanopathies while white matter abnormalities without major cognitive involvement tend to be seen in the laminin alpha-2-deficient subtype.
Meckel syndrome type 1
MedGen UID:
811346
Concept ID:
C3714506
Disease or Syndrome
Meckel syndrome, also known as Meckel-Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of primary cilia during early embryogenesis. There is extensive clinical variability and controversy as to the minimum diagnostic criteria. Early reports, including that of Opitz and Howe (1969) and Wright et al. (1994), stated that the classic triad of Meckel syndrome comprises (1) cystic renal disease; (2) a central nervous system malformation, most commonly occipital encephalocele; and (3) polydactyly, most often postaxial. However, based on a study of 67 patients, Salonen (1984) concluded that the minimum diagnostic criteria are (1) cystic renal disease; (2) CNS malformation, and (3) hepatic abnormalities, including portal fibrosis or ductal proliferation. In a review of Meckel syndrome, Logan et al. (2011) stated that the classic triad first described by Meckel (1822) included occipital encephalocele, cystic kidneys, and fibrotic changes to the liver. Genetic Heterogeneity of Meckel Syndrome See also MKS2 (603194), caused by mutation in the TMEM216 gene (613277) on chromosome 11q12; MKS3 (607361), caused by mutation in the TMEM67 gene (609884) on chromosome 8q; MKS4 (611134), caused by mutation in the CEP290 gene (610142) on chromosome 12q; MKS5 (611561), caused by mutation in the RPGRIP1L gene (610937) on chromosome 16q12; MKS6 (612284), caused by mutation in the CC2D2A gene (612013) on chromosome 4p15; MKS7 (267010), caused by mutation in the NPHP3 (608002) gene on chromosome 3q22; MKS8 (613885), caused by mutation in the TCTN2 gene (613846) on chromosome 12q24; MKS9 (614209), caused by mutation in the B9D1 gene (614144) on chromosome 17p11; MKS10 (614175), caused by mutation in the B9D2 gene (611951) on chromosome 19q13; MKS11 (615397), caused by mutation in the TMEM231 gene (614949) on chromosome 16q23; MKS12 (616258), caused by mutation in the KIF14 gene (611279) on chromosome 1q32; and MKS13 (617562), caused by mutation in the TMEM107 gene (616183) on chromosome 17p13.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 13
MedGen UID:
815372
Concept ID:
C3809042
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is a autosomal recessive disorder associated with severe neurologic defects and resulting in early infantile death. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Buysse et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
MEND syndrome
MedGen UID:
905986
Concept ID:
C4085243
Disease or Syndrome
Male EBP disorder with neurologic defects is an X-linked recessive disorder representing a continuous phenotypic spectrum with variable manifestations associated with a defect in sterol biosynthesis. Features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. Not all patients show all features, and the severity is highly variable. Molecular studies indicate that affected males are hemizygous for a nonmosaic hypomorphic EBP allele. Carrier females are generally clinically asymptomatic, but may show biochemical abnormalities (summary by Arnold et al., 2012 and Barboza-Cerda et al., 2014).
Ritscher-schinzel syndrome 2
MedGen UID:
897005
Concept ID:
C4225419
Disease or Syndrome
Ritscher-Schinzel syndrome-2 is an X-linked recessive syndromic form of intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities (summary by Kolanczyk et al., 2015). For a discussion of genetic heterogeneity of Ritscher-Schinzel syndrome, see RTSC1 (220210).
Trichothiodystrophy 5, nonphotosensitive
MedGen UID:
899675
Concept ID:
C4225420
Disease or Syndrome
Coffin-Siris syndrome 5
MedGen UID:
934755
Concept ID:
C4310788
Disease or Syndrome
Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Heart and brain malformation syndrome
MedGen UID:
934760
Concept ID:
C4310793
Disease or Syndrome
Heart and brain malformation syndrome is a severe autosomal recessive multiple congenital anomaly syndrome characterized by profoundly delayed psychomotor development, dysmorphic facial features, microphthalmia, cardiac malformations, mainly septal defects, and brain malformations, including Dandy-Walker malformation (summary by Shaheen et al., 2016).
Noonan syndrome-like disorder with loose anagen hair 2
MedGen UID:
1376945
Concept ID:
C4479577
Disease or Syndrome

Recent clinical studies

Etiology

Gai N, Jiang C, Zou YY, Zheng Y, Liang DS, Wu LQ
Clin Chim Acta 2016 Jul 1;458:1-4. Epub 2016 Apr 19 doi: 10.1016/j.cca.2016.04.018. PMID: 27106665
Mauritz MW, van de Sande R, Goossens PJ, van Achterberg T, Draijer N
J Trauma Dissociation 2014;15(5):588-606. doi: 10.1080/15299732.2014.938213. PMID: 24983777
Jha VC, Kumar R, Srivastav AK, Mehrotra A, Sahu RN
Childs Nerv Syst 2012 Jun;28(6):861-7. Epub 2012 Apr 4 doi: 10.1007/s00381-012-1734-8. PMID: 22476659
Yahyaoui R, Espinosa MG, Gómez C, Dayaldasani A, Rueda I, Roldán A, Ugarte M, Lastra G, Pérez V
Mol Genet Metab 2011 Nov;104(3):414-6. Epub 2011 May 12 doi: 10.1016/j.ymgme.2011.05.003. PMID: 21641254
Salihu HM, Kornosky JL, Alio AP, Druschel CM
J Natl Med Assoc 2009 May;101(5):456-61. PMID: 19476199

Diagnosis

Tranos P, Dervenis N, Kiouras S
Semin Ophthalmol 2017;32(4):501-503. Epub 2016 Apr 14 doi: 10.3109/08820538.2015.1123732. PMID: 27077329
Infante JR, Garcia L, Rayo JI, Serrano J, Dominguez ML, Moreno M
Clin Nucl Med 2016 Jan;41(1):e58-9. doi: 10.1097/RLU.0000000000000871. PMID: 26053730
Buonaguro EF, Cimmarosa S, de Bartolomeis A
Riv Psichiatr 2014 Mar-Apr;49(2):100-2. doi: 10.1708/1461.16151. PMID: 24770576
Kusumoto Y, Shinozuka O
Spec Care Dentist 2014 May-Jun;34(3):151-5. Epub 2013 Jul 16 doi: 10.1111/scd.12044. PMID: 24712511
Zhang W, Chen M, Zhang W
J Craniofac Surg 2013 Jul;24(4):1457-9. doi: 10.1097/SCS.0b013e31828f2ef2. PMID: 23851831

Therapy

Lee HC, Choi JW, Lee JY, Phi JH, Kim SK, Cho BK, Wang KC
Childs Nerv Syst 2017 Apr;33(4):665-670. Epub 2016 Nov 7 doi: 10.1007/s00381-016-3293-x. PMID: 27822765
Tranos P, Dervenis N, Kiouras S
Semin Ophthalmol 2017;32(4):501-503. Epub 2016 Apr 14 doi: 10.3109/08820538.2015.1123732. PMID: 27077329
Williams AJ, Wang Z, Taylor SF
Neurocase 2016 Oct;22(5):472-475. Epub 2016 Sep 23 doi: 10.1080/13554794.2016.1237657. PMID: 27662527
Reeder MR, Botto LD, Keppler-Noreuil KM, Carey JC, Byrne JL, Feldkamp ML; National Birth Defects Prevention Study.
Am J Med Genet A 2015 Sep;167A(9):2009-16. Epub 2015 May 1 doi: 10.1002/ajmg.a.37124. PMID: 25941000
Mauritz MW, van de Sande R, Goossens PJ, van Achterberg T, Draijer N
J Trauma Dissociation 2014;15(5):588-606. doi: 10.1080/15299732.2014.938213. PMID: 24983777

Prognosis

Jha VC, Kumar R, Srivastav AK, Mehrotra A, Sahu RN
Childs Nerv Syst 2012 Jun;28(6):861-7. Epub 2012 Apr 4 doi: 10.1007/s00381-012-1734-8. PMID: 22476659
Yahyaoui R, Espinosa MG, Gómez C, Dayaldasani A, Rueda I, Roldán A, Ugarte M, Lastra G, Pérez V
Mol Genet Metab 2011 Nov;104(3):414-6. Epub 2011 May 12 doi: 10.1016/j.ymgme.2011.05.003. PMID: 21641254
Kontopoulos EV, Quintero RA, Salihu HM, Bornick PW, Allen MH
J Matern Fetal Neonatal Med 2008 Nov;21(11):839-42. doi: 10.1080/14767050802302967. PMID: 18979394
Salihu HM, Kornosky JL, Druschel CM
Fetal Diagn Ther 2008;24(2):155-60. Epub 2008 Jul 17 doi: 10.1159/000142146. PMID: 18648217
Maria BL, Bozorgmanesh A, Kimmel KN, Theriaque D, Quisling RG
J Child Neurol 2001 Oct;16(10):751-8. doi: 10.1177/088307380101601008. PMID: 11669349

Clinical prediction guides

Zhu L, Xie L
Medicine (Baltimore) 2017 Dec;96(51):e8626. doi: 10.1097/MD.0000000000008626. PMID: 29390414Free PMC Article
Kusumoto Y, Shinozuka O
Spec Care Dentist 2014 May-Jun;34(3):151-5. Epub 2013 Jul 16 doi: 10.1111/scd.12044. PMID: 24712511
Litzman J, Bucková H, Ventruba J, Holcíková A, Mikyska P, Lokaj J
Acta Paediatr 2003 Jul;92(7):861-4. PMID: 12892171
Poetke M, Bültmann O, Berlien HP
Eur J Pediatr Surg 2000 Apr;10(2):125-9. doi: 10.1055/s-2008-1072340. PMID: 10877082
Miyamori T, Okabe T, Hasegawa T, Takinami K, Matsumoto T
Neurol Med Chir (Tokyo) 1999 Oct;39(11):766-8. PMID: 10598445

Recent systematic reviews

Alp MY, Çebi AH, Seyhan S, Cansu A, Aydin H, Ikbal M
Genet Couns 2016;27(1):43-9. PMID: 27192891
D'Antonio F, Khalil A, Garel C, Pilu G, Rizzo G, Lerman-Sagie T, Bhide A, Thilaganathan B, Manzoli L, Papageorghiou AT
Ultrasound Obstet Gynecol 2016 Jun;47(6):690-7. Epub 2016 May 10 doi: 10.1002/uog.14900. PMID: 25970099
Liu S, Hong X, Shen C, Shi Q, Wang J, Xiong F, Qiu Z
BMC Med Genet 2015 Apr 21;16:26. doi: 10.1186/s12881-015-0171-4. PMID: 25896430Free PMC Article
Zandian A, Haffner M, Johnson J, Rozzelle CJ, Tubbs RS, Loukas M
Childs Nerv Syst 2014 Apr;30(4):571-8. Epub 2013 Dec 28 doi: 10.1007/s00381-013-2344-9. PMID: 24374638
Poetke M, Frommeld T, Berlien HP
Eur J Pediatr Surg 2002 Dec;12(6):366-74. doi: 10.1055/s-2002-36849. PMID: 12548487

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center