X‐linked ichthyosis: Clinical and molecular findings in 35 Italian patients

Abstract

Recessive X-linked ichthyosis (XLI), the second most common ichthyosis, is caused by mutations in the STS gene encoding the steroid sulfatase enzyme. A complete deletion of the STS gene is found in 85%-90% of cases. Rarely, larger deletions involving contiguous genes are detected in syndromic patients. We report the clinical and molecular genetic findings in a series of 35 consecutive Italian male patients. All patients underwent molecular testing by MLPA or aCGH, followed, in case of negative results, by next-generation sequencing analysis. Neuropsychiatric, ophthalmological and paediatric evaluations were also performed. Our survey showed a frequent presence of disease manifestations at birth (42.8%). Fold and palmoplantar surfaces were involved in 18 (51%) and 7 (20%) patients, respectively. Fourteen patients (42%) presented neuropsychiatric symptoms, including attention-deficit hyperactivity disorder and motor disabilities. In addition, two patients with mental retardation were shown to be affected by a contiguous gene syndrome. Twenty-seven patients had a complete STS deletion, one a partial deletion and 7 carried missense mutations, two of which previously unreported. In addition, a de novo STS deletion was identified in a sporadic case. The frequent presence of palmoplantar and fold involvement in XLI should be taken into account when considering the differential diagnosis with ichthyosis vulgaris. Our findings also underline the relevance of involving the neuropsychiatrist in the multidisciplinary management of XLI. Finally, we report for the first time a de novo mutation which shows that STS deletion can also occur in oogenesis.

X‐linked ichthyosis: Molecular findings in four pedigrees with inconspicuous clinical manifestations

“…XLI is an X‐linked, recessively inherited disorder of cutaneous keratinization. Since the STS gene escapes X chromosome inactivation, female patients with XLI contain the same amounts of STS with healthy males, in whom skin scales are rare . However, male patients with XLI often have polygonal, semitransparent, and fine scales on the skin at birth or soon after birth, and the scales gradually become deep dark and rough with age.…”

A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients

“…Family in our study belongs to a village in Pakistan and the male members work as farmers thus having a lot of sun-exposure, resulting in complete disease resolution during summer. Hypohidrosis is also known to be present due to keratotic plugs filling in sweat glands orifices [33]. The focus of treatment is lubrication, cutaneous hydration, and keratolysis, it should also include topical moisturizers and topical retinoids.…”

Next Generation Sequencing Uncovers a Rare Case of X-linked Ichthyosis in an Adopted Girl Homozygous for a Novel Nonsense Mutation in the STS Gene

“…In our adopted girl, the unavailability of personal and family histories, in particular the patient's age at disease onset, its course, and the likely presence of an affected father, have hampered clinical diagnosis. On the other hand, sparing of palmoplantar surfaces is considered one of the most reliable clinical findings supporting a diagnosis of XLI (1,4,13). Clinical features were detailed in only 4 out of 8 previously reported cases of XLI in females (8,10,11).…”

“…It almost exclusively affects males and the estimated prevalence ranges from 1 in 1,500 to 1 in 6,000 males (1)(2)(3). XLI is caused by mutations in the STS gene on chromosome Xp22.31 encoding for the steroid sulfatase (STS) enzyme (1,4). Most patients (85-90%) carry a genomic deletion comprising the entire STS gene, while point mutations or partial deletions account for about 10% of cases.…”

“…Most patients (85-90%) carry a genomic deletion comprising the entire STS gene, while point mutations or partial deletions account for about 10% of cases. XLI manifests more frequently in the neonatal period with generalized whitish, lamellar desquamation, which over time is replaced by the typical polygonal, dark scales that are more prominent on legs and arms (1,4).…”