Rothmund-Thomson syndrome type 1 caused by biallelic ANAPC1 gene mutations.

Background

Rare syndromic skin disorders may represent a diagnostic challenge.

Aims

We report a unique case associating cutaneous manifestations and developmental delay.

Materials & Methods

The affected 14 months old boy had poikiloderma, facial dysmorphism with deep-set eyes, atrichia, as well as nail dysplasia and non-descended testes. In addition, his psychomotor development was delayed. Exome sequencing and molecular karyotyping via array-CGH (oligo-array, 180k Agilent, design 22060) were performed.

Results

Mutations in RECQL4 (found in patients with RTS2) were first excluded. In the ANAPC1 gene, a novel combination of a recurrent intronic mutation (c.2705-198C>T) and a deletion of the second ANAPC1 allele was detected, thus confirming the clinical diagnosis of RTS1. The deletion on chromosome 2q13 comprised further genes and spanned 1,7 megabases. Heterozygous deletions in this region are known as 2q13 microdeletion syndrome and are associated with developmental delay, autism and facial dysmorphism.

Discussion

The genetic findings most probably explain both, the RTS1 features and the developmental delay. Genetic diagnosis in RTS is indispensable to confirm the specific subtype and its associated risks: juvenile cataracts are features of RTS1 (ANAPC1 gene), whereas a high risk of osteosarcoma is part of RTS2 (RECQL4 gene). Thus, the patient described here is at high risk for the development of juvenile cataracts and requires regular ophthalmologic examination.

Conclusion

This case report underlines the necessity of thorough clinical diagnosis prior to genetic diagnosis of RTS1, since the recurrent intronic ANAPC1 mutation is otherwise missed.

Informations de copyright

© 2021 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Déclaration de conflit d'intérêts

The authors declare that there is no conflict of interests.