Expanding the Clinical Spectrum of Sotos Syndrome in a Patient with the New “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]” NSD1 Missense Mutation and Complex Skin Hamartoma
Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy
Medical Genetics Unit, S. Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy
Laboratory of Human Genetics, Galliera Hospital, Mura delle Cappuccine, 14, 16128 Genoa, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3189; https://doi.org/10.3390/ijms19103189
Received: 5 September 2018 / Revised: 7 October 2018 / Accepted: 8 October 2018 / Published: 16 October 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000–1:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a “café-au-lait” spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]”, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient’s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.