Abstract

Background: X-linked ichthyosis (XLI) (steroid sulfatase deficiency) is caused by deletions or point mutations of the steroid sulfatase (STS) gene on chromosome Xp22.32. Deletions of this region can be associated with cognitive behavioural difficulties including autism. Animal work suggests the STS gene may be involved in attentional processes. We have therefore undertaken a systematic study of autism and attention deficit hyperactivity disorder (ADHD) in boys with XLI.

Methods: Cases of XLI were recruited from families originally ascertained when pregnancies with STS deficiency were identified through a routine maternal screening programme. Boys with XLI were assessed for ADHD and autism using standardised questionnaires and interviews. Deletions of the STS gene were identified and characterised by analysis of genomic DNA and/or fluorescent in situ hybridisation.

Results: 25 boys with XLI were assessed for autism and ADHD. 40% fulfilled DSM-IV criteria for a diagnosis of ADHD, 80% of which were inattentive subtype. ADHD diagnoses were present in those with both deletions and presumed point mutations of STS. Additionally, five boys, from three unrelated families, fulfilled criteria for an autistic spectrum disorder or related language/communication difficulty, and all had an unusually large deletion of the STS gene with loss of the neuroligin 4 (NLGN4) gene. None of the boys with the typical deletion or presumed point mutations of STS demonstrated autistic difficulties.

Conclusions: STS deficiency may be a risk factor for ADHD with predominantly inattentive symptoms. Boys with XLI and large deletions encompassing STS and NLGN4 are at increased risk of developing autism and related disorders.