agenesis of the corpus callosum

Donnai-Barrow Syndrome

Clinical Characteristics

Ocular Features

A number of ocular features have been described in this disorder, including telecanthus, hypertelorism, and iris hypoplasia.  Patients may have marked iris transillumination.  Myopia is commonly present and retinal detachments are a risk.  Several patients had iris colobomas.  Cataracts, small optic nerves, and macular hypoplasia have been reported as well.  The lid fissures usually slant downward. 

Systemic Features

The facial dysmorphology, in addition to the periocular malformations, includes a prominent brow or frontal bossing, posterior rotation of the ears, a flat nasal bridge and a short nose.  Sensorineural hearing loss is universal and at least some patients have complete or partial agenesis of the corpus callosum, and an enlarged anterior fontanel.  Diaphragmatic and umbilical hernias often occur together.  Low-molecular-weight proteinuria in the absence of aminoaciduria is a frequent feature.  Developmental delays are often seen but occasional patients have normal intellect.  Rare patients have seizures. 

Genetics

This is a rare autosomal recessive disorder caused by homozygous mutations in the LRP2 (low-density lipoprotein receptor-related protein 2 or megalin) gene located at 2q24-q31.  Some patients have an ocular phenotype resembling the Stickler syndrome.

Treatment Options

Treatment is focused on specific manifestations such as cataract and retinal detachment surgery. Patients need to be monitored throughout life for retinal disease.  Omphaloceles and diaphragmatic hernias need to be repaired.  Hearing aids may be beneficial. 

References

Schrauwen I, Sommen M, Claes C, Pinner J, Flaherty M, Collins F, Van Camp G. Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome. Clin Genet. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23992033.

PubMed ID: 
23992033

Pober BR, Longoni M, Noonan KM. A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome: clinical features and differential diagnosis. Birth Defects Res A Clin Mol Teratol. 2009 Jan;85(1):76-81. Review.

PubMed ID: 
19089858

Patel N, Hejkal T, Katz A, Margalit E. Ocular manifestations of Donnai-Barrow syndrome. J Child Neurol. 2007 Apr;22(4):462-4.

PubMed ID: 
17624530

Chassaing N, Lacombe D, Carles D, Calvas P, Saura R, Bieth E. Donnai-Barrow syndrome: four additional patients. Am J Med Genet A. 2003 Sep 1;121A(3):258-62. Review.

PubMed ID: 
12923867

Schowalter DB, Pagon RA, Kalina RE, McDonald R. Facio-oculo-acoustico-renal (FOAR) syndrome: case report and review. Am J Med Genet. 1997 Mar 3;69(1):45-9; discussion 44. Review.

PubMed ID: 
9066882