Link: https://www.ncbi.nlm.nih.gov/pubmed/20301732

Donnai-Barrow Syndrome.
AuthorsLongoni M1, Kantarci S2, Donnai D3, Pober BR4.
EditorsIn: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. SourceGeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2008 Aug 28 [updated 2018 Nov 21].
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Excerpt
CLINICAL CHARACTERISTICS:
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (large anterior fontanel, wide metopic suture, widow's peak, markedly widely spaced eyes, enlarged globes, downslanted palpebral fissures, posteriorly rotated ears, depressed nasal bridge, and short nose. Ocular complications include high myopia, retinal detachment, retinal dystrophy, and progressive vision loss. Additional common features include agenesis of the corpus callosum, sensorineural hearing loss, intellectual disability, and congenital diaphragmatic hernia and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.

DIAGNOSIS/TESTING:
The diagnosis of DBS is established in a proband with: the characteristic clinical features and a distinctive pattern of low-molecular-weight proteinuria; and/or biallelic pathogenic variants in LRP2 identified by molecular genetic testing.

MANAGEMENT:
Treatment of manifestations: Surgical repair of diaphragmatic hernia and/or omphalocele; corrective lenses for myopia; preventive treatments for retinal detachment; hearing aids and/or cochlear implants for hearing loss; antiepileptic drugs for seizures; supplementation as needed for low serum vitamins A and D; education tailored to degree of intellectual, visual, and hearing abilities. Surveillance: Ophthalmologic surveillance to monitor for retinal detachment; serial audiologic examinations; serial measurement of renal function including blood urea nitrogen and serum creatinine concentrations, urinalysis, and serum vitamin A and D; monitor developmental progress and educational needs.

GENETIC COUNSELING:
DBS is inherited in an autosomal recessive manner. In general, the parents of an affected child are obligate heterozygotes with each carrying one pathogenic variant; one instance of uniparental disomy has been reported. When both parents are known to be carriers of a pathogenic variant, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If the pathogenic variants in the family are known, carrier testing for at-risk relatives and prenatal testing of pregnancies at increased risk are possible.

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Sections
Summary
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
References
Chapter Notes
PMID: 20301732
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