Baraitser-Winter syndrome-1

Coloboma, Ptosis, Hypertelorism, and Global Delay

Clinical Characteristics
Ocular Features: 

The ocular phenotype includes ptosis, hypertelorism, iris coloboma and prominent epicanthal folds with epicanthus inversus.  The coloboma may be unilateral and involve other portions of the uveal tract. The orbits have been described as shallow.  At least one patient has been described as having microphthalmia and microcornea.

Systemic Features: 

The systemic features reported include severe global delay, a broad nasal bridge, and short stature.  Physical growth delay, mental retardation, short neck, low-set ears, and low posterior hairline have been noted.  Males may have a micropenis and undescended testicles.  The pinnae may be malformed and rotated posteriorly. Several patients had a hearing deficit.

CT scans have shown microcephaly with pachygyria and or even virtual agyria of the frontal, temporal, and parietal lobes.

Genetics

This condition is caused by heterozygous mutations in the ACTG1 gene (17q25.3) and therefore transmitted in an autosomal dominant pattern.  Sibs but no parental consanguinity has been reported.  Both sexes are affected.

Mutations in the same gene are responsible for a somewhat similar condition known as Baraister-Winter 2 syndrome (614583).

Temtamy syndrome (218340) has some similar features but is caused by mutations in C12orf57 (12p13).  In addition to microphthalmia and colobomas, intractable seizures, global delay and abnormalities of the corpus callosum are present.

Several patients that may have had this syndrome have had pericentric inversions of chromosome 2: inv(2)(p12q14).  The PAX8 gene maps to the distal breakpoint of this inversion and may play a role as the location of a recessive mutation or as part of a submicroscopic inversion.  No parent-child transmission has been reported.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures

Platzer K, Huning I, Obieglo C, Schwarzmayr T, Gabriel R, Strom TM, Gillessen-Kaesbach G, Kaiser FJ. Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. Am J Med Genet A. 2014 May 5. [Epub ahead of print].

PubMed ID: 
24798461
Subscribe to RSS - Baraitser-Winter syndrome-1