Donnai-Barrow-Syndrome Q87.-

Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (large anterior fontanel, broad-based "pointed hairline" metopic suture, "widow's peak" hair, widely spaced eyes, enlarged eyeballs, down-slanting palpebral fissures, posteriorly rotated ears, flat nasal bridge and short nose). Eye complications include high myopia, retinal detachment, retinal dystrophy and progressive vision loss. Other common features include agenesis of the corpus callosum, sensorineural hearing loss, mental retardation and congenital diaphragmatic hernia and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.

The diagnosis of DBS is made when a subject has the characteristic clinical features and a distinct pattern of low molecular weight proteinuria and/or when biallelic pathogenic variants in the LRP2 gene (2q31.1) have been identified by molecular genetic testing.

Treatment of symptoms: Surgical repair of diaphragmatic hernias and/or omphaloceles; 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 vitamin A and vitamin D levels; education tailored to the level of intellectual, visual and hearing abilities.

Monitoring: Ophthalmologic monitoring to watch for retinal detachment; regular audiologic examinations; regular measurement of kidney function including blood urea nitrogen and serum creatinine levels, urinalysis and measurement of serum vitamin A and D; monitoring of developmental progress and educational needs.

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

1. Longoni M et al (2008) Donnai-Barrow syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. PMID: 20301732.
2. Robinson MK et al. (2021) A Case Report of Donnai-Barrow Syndrome. Adv Neonatal Care 21:133-141.