Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation.

Contiguous gene syndromes are an interesting clinical phenomenon, resulting from interstitial or terminal deletions of several adjacent genes. The phenotype results in a combination of two or more monogenic disorders and relates clinical findings to corresponding genotypes. We present the case of a male patient with Kallmann syndrome (KS), X-linked ichthyosis (XLI) and X-linked mental retardation (MRX). He was referred at the age of 15.4 years for delayed puberty and obesity. He had a previous history of pyloric stenosis, bilateral orchidopexy and surgical correction of a pes equinovarus adductus. On physical examination, generalised ichthyosis and hypoplastic external genitalia were found. KS was evident with hypogonadotropic hypogonadism, hyposmia and a hypoplastic anlage of the olfactory tract in magnetic resonance imaging. Lipoprotein electrophoresis, and lack of steroid sulfatase and arylsulfatase-C activity in leucocytes confirmed XLI. DNA investigation established an interstitial deletion in Xp22.3 involving the Kallmann (KAL) gene, the steroid sulfatase (STS) gene and a putative mental retardation locus (MRX). The novel MRX locus maps to a 1-Mb region between DXS1060 and GS1.