OMIM ID:
Donnai-Barrow Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
A number of ocular features have been described in this disorder, including telecanthus, hypertelorism, and iris hypoplasia with 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
Inheritance
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 (609508).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.