Clinical and behavioural phenotype in a contiguous gene deletion syndrome at Xp22.3

We report a 6-year-old boy with ocular albinism, psychomotor retardation and behavioural abnormalities similiar to attention deficit hyperactivity disorder (ADHD). He was born with a club foot on the right side and showed dry skin with scaling. Growth parameters were on the 3rd percentile. Facial dysmorphism was noted with blepharophimosis, narrow palpebral fissures, flat philtrum, thin upper lip and large deep set ears. The boy, his mother and his maternal grandmother have severe hyperopia.

The presence of ocular albinism, ichthyosis and ADHD suggested a contiguous gene deletion syndrome with Xp deletion. The GTG-karyotype showed no structural abnormality of the X-chromosome and FISH analysis with the subtelomeric probe could exclude a terminal deletion. In contrast FISH analysis with the Kallmann probe (LSI Kal) clearly demonstrated a deletion of this region. Consequently fine mapping studies were performed. The distal breakpoint was mapped between the markers DXS7100 and DXS7099. The proximal breakpoint was mapped between the markers KIAA 1280 and DXS7103 indicating that the STS (ichthyosis), KAL1 (Kallmann syndrome) and OA1 (ocular albinism) genes are deleted in this patient. Some of the other genes located in the deleted region such as NLGN4 (neuroligin) or VCX might be responsible for the psychomotor retardation and the characteristic behavioural abnormalities also diagnosed for this boy. The same Xp22.3 deletion with the same distal and proximal breakpoints was found in the mother.