Oral 4, X-linked ichthyosis with a contiguous gene defect in three successive generations

Abstract

X-linked ichthyosis (XLI) is most commonly caused by deletions in the steroid sulphatase (STS) gene. Larger chromosomal deletions may also result in Kallmann syndrome (KS) and mental retardation (MR).1 We present the clinical features of such a contiguous gene defect in three generations of one family. A 7-month-old boy presented with dry skin since birth. Four male family members had similar skin changes, anosmia, delayed puberty and mild MR. Two of these males had only one kidney. On examination he had symmetrical scaling on the trunk and extensor limbs and bilateral undescended testes. Cytogenetic analysis showed an interstitial deletion of the distal short arm of the X-chromosome, with breakpoints at Xp22.31 and Xp22.33. Fluorescent in situ hybridization studies confirmed deletions of the STS and KS genes. Further studies using hybridization to a high-resolution microarray are under way. A renal ultrasound scan has shown a probable absent left kidney. A dimercaptosuccinic acid scan is awaited. The child's family has received genetic counselling and he is now under the care of paediatrics and endocrinology. Both testes have descended in response to a course of human chorionic gonadotrophin injections. At 23 months he shows global developmental delay and displays synkinesis (mirror movements). This family illustrates the importance of considering contiguous gene defects in XLI. Delay in diagnosis can result in infertility, late onset of puberty, osteoporosis and failure to recognize special educational needs. Reference 1 Paige DG, Emilion GG, Bouloux PMG, Harper JI. A clinical and genetic study of X-linked recessive ichthyosis and contiguous gene defects. Br J Dermatol 1994; 131:622–9.