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Disease Profile

Dandy-Walker like malformation with atrioventricular septal defect

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cranio-cerebello-cardiac dysplasia; 3C syndrome; Craniocerebellocardiac dysplasia;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 7

Definition
Cranio-cerebello-cardiac (3C) syndrome is a rare multiple congenital anomalies syndrome characterized by craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies (see these terms).

Epidemiology
To date < 50 cases have been described. The syndrome appears to be panethnic.

Clinical description
3C syndrome is a congenital disorder characterized by distinctive craniofacial features including, in decreasing frequency, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge, prominent occiput, prominent forehead, cleft palate, micrognathia, ocular coloboma. Additional craniofacial features encompass nevus flammeus (on forehead), low posterior hairline, sparse scalp hair, eyebrows and eyelashes, open mouth with protruding tongue, and short neck. In 80% of cases, cerebellar anomalies are present and include primarily Dandy-Walker malformation or Dandy-Walker variant, cerebellar vermis hypoplasia and enlargement of cisterna magma. Affected individuals have gross motor and speech delay and intellectual disability. The cardiovascular anomalies include atrial and ventricular septal defects, patent arterial duct, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart syndrome (see these terms), aortic or pulmonary stenosis, and other valvular anomalies. Postnatal short stature is noted in most patients, and growth hormone deficiency has been reported in two patients. Additional anomalies, noted in >10% of patients, include feeding difficulties, single umbilical artery, small hands with single transverse crease, camptodactyly, equinovarus deformity, hydronephrosis, shallow scrotum, undescended testis, cryptorchidism, micropenis, hypospadias, nail hypoplasia, hearing loss, malrotation of the gut. Skeletal defects may be present with rib and vertebral anomalies (hemivertebrae). Rarely observed features include ocular (congenital glaucoma, optic nerve atrophy with eyelid ptosis, heteochromatic iris, posterior embryotoxon), renal (multicystic dysplastic kidney, horseshoe kidneys, unilateral renal agenesis) and anal (anal atresia, anteriorly placed anus malformations) anomalies. Single occurrences of renal hypoplasia, nipple hypoplasia, penile hypoplasia, unilateral adrenal aplasia, immunodeficiency have also been reported.

Etiology
The exact etiology is still unknown but mutations in KIAA0196 (8q24.13; coding for strumpellin) have been identified in a First Nations cohort and these mutations may be involved in the pathophysiology of 3C syndrome.

Diagnostic methods
The diagnostic criteria for 3C syndrome include congenital heart malformation(s) other than isolated patent arterial duct; Dandy-Walker malformation, cerebellar vermis hypoplasia, or enlarged cisterna; and cleft palate, ocular coloboma or four of the following: prominent occiput, prominent forehead, hypertelorism, micrognathia, downslanting palpebral fissures, depressed nasal bridge, low-set ears.

Differential diagnosis
Differential diagnosis includes Joubert syndrome, Ellis Van Creveld syndrome, Cornelia de Lange syndrome, distal monosomy 6p (see these terms) and Dandy Walker malformation.

Antenatal diagnosis
Prenatal diagnosis may be suspected after an ultrasound examination revealing characteristic major structural anomalies of 3C syndrome. Prenatal testing is available for families in which the disease-causing mutations have been previously identified.

Genetic counseling
Sporadic and familial cases have been reported. Transmission is autosomal recessive. Phenotypic variability exists between siblings.

Management and treatment
Management is mainly symptomatic and multidisciplinary approaches including educational programs, physical, occupational, and speech therapy may help to improve hypotonia and reduce motor developmental delay. Cardiac malformation requires specific care, often surgery.

Prognosis
Prognosis is determined by the cardiovascular malformation. Motor delay is common and associated with hypotonia secondary to cerebellar anomalies.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the fontanelles or cranial sutures
0000235
Dandy-Walker malformation
0001305
Frontal bossing
0002007
Global developmental delay
0001263
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscular hypotonia
Low or weak muscle tone
0001252
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal mitral valve morphology
0001633
Abnormal tricuspid valve morphology
0001702
Aortic valve stenosis
Narrowing of aortic valve
0001650
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Atrioventricular canal defect
0006695
Cleft palate
Cleft roof of mouth
0000175
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplastic left heart
Underdeveloped left heart
0004383
Kyphosis
Hunched back
Round back

[ more ]

0002808
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Scoliosis
0002650
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Short stature
Decreased body height
Small stature

[ more ]

0004322
Tetralogy of Fallot
0001636
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
5%-29% of people have these symptoms
Abnormality of neuronal migration
0002269
Abnormality of the hip bone
Abnormality of the hips
0003272
Adrenal hypoplasia
Small adrenal glands
0000835
Anal atresia
Absent anus
0002023
Aplasia/Hypoplasia of the nipples
Absent/small nipples
Absent/underdeveloped nipples

[ more ]

0006709
Brachydactyly
Short fingers or toes
0001156
Chorioretinal coloboma
Birth defect that causes a hole in the innermost layer at the back of the eye
0000567
Ectopic anus
Abnormal anus position
0004397
Facial hemangioma
0000329
Feeding difficulties in infancy
0008872
Finger syndactyly
0006101
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Glaucoma
0000501
Hand polydactyly
Extra finger
0001161
Hemivertebrae
Missing part of vertebrae
0002937
Hydronephrosis
0000126
Hypoplasia of penis
Underdeveloped penis
0008736
Hypoplastic fingernail
Small fingernail
Underdeveloped fingernail

[ more ]

0001804
Hypospadias
0000047
Inguinal hernia
0000023
Intestinal malrotation
0002566
Iris coloboma
Cat eye
0000612
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Dandy-Walker like malformation with atrioventricular septal defect. Click on the link to view a sample search on this topic.

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