Phenotypic and genetic spectrum of incontinentia pigmenti - a large case series

Background and objectives: Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. Patients and methods: This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. Results: The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. Conclusions: In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Automated summary

Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin and other neuroectodermal tissues. This study involving 30 patients revealed a range of cutaneous and extracutaneous manifestations, with common genetic deletions and other pathogenic variants identified. Regular evaluation of extracutaneous involvement is recommended for diagnosis and monitoring.