A New Locus On Chromosome 14 Causes Waardenburg Anophthalmia Syndrome

Abstract

Purpose: : To identify the genetic origin of Waardenburg anophthalmia syndrome.

Methods: : We performed a genome-wide SNPs array analysis in a consanguineous family of Egyptian origin with two affected children. Complete systemic and ophthalmic examination was performed, as well as cerebral MRI, kidney and skeletal X-rays.

Results: : The first child was a 12-year-old girl born to healthy consanguineous parents when last seen at our clinics. At birth, her father was 33 and her mother 30 years old. The second affected child was 8 years old. Both affected had global delay in developmental milestones. Binet test performed on the youngest child at 7 years of age gave a score of 80 and her older sister was similarly mentally retarded. On examination, both had short palpebral fissures and bilateral anophthalmia, confirmed by ultrasonography. Skeleton abnormalities included malar flattening, high palate, bilateral proximal placement of thumb, bilateral F45 osseous syndactyly, bilateral F5 radial clinodactyly, bilateral camptodactyly of F15, absent ray in both feet with sandal gap and pes planum, and mild scoliosis. Orbital and brain MRI were performed in both girls as well. No eye globe or cysts were reported on orbital MRI, but normal extraocular muscles in signal and size were present. Brain MRI showed complete absence of eye globes, optic nerves, chiasma and optic tracts. Abdominal ultrasound did not show any renal malformations. Linkage analysis identified a homozygous region of 14Mb on chromosome 14. This region contains more than 100 genes that are currently being examined.

Conclusions: : Anophthalmia-acromelic syndrome also known as anophthalmia-Waardenburg is an autosomal recessive rare disease. In addition to the previously discovered locus on chromosome 10 we identified a new locus on chromosome 14. Our analysis shows that anophthalmia-Waardenburg syndrome is genetically heterogeneous.

Keywords: development • gene mapping • genetics