Hamamy Syndrome

A number sign (#) is used with this entry because of evidence that severe hypertelorism with midface prominence, myopia, mental retardation, and bone fragility can be caused by homozygous mutation in the IRX5 gene (606195) on chromosome 16q11.2.

Clinical Features

Hamamy et al. (2007) described 2 brothers, born to double first-cousin Jordanian Arab parents, with severe hypertelorism, upslanting palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Both had severe myopia, mild to moderate sensorineural hearing loss, and borderline intelligence. Their father had mild hypertelorism, and they had a phenotypically normal younger sister. Hamamy et al. (2007) concluded that this was a previously unrecognized autosomal or X-linked recessive syndrome.

Mapping

In 2 consanguineous families segregating an autosomal recessive craniofacial disorder, 1 of which was originally reported by Hamamy et al. (2007), Bonnard et al. (2012) performed identical-by-descent homozygosity mapping and identified a single 9.2-Mb candidate locus on chromosome 16q12.2-q21.

Molecular Genetics

In 5 affected individuals from 2 consanguineous families, 1 Turkish and the other a Jordanian family previously reported by Hamamy et al. (2007), with an autosomal recessive craniofacial syndrome mapping to chromosome 16q12.2-q21, Bonnard et al. (2012) screened 73 candidate genes and identified 2 homozygous missense mutations in the IRX5 gene (606195.0001 and 606195.0002) that segregated with disease in each family. They suggested that the disorder be designated 'Hamamy syndrome.'