Endocrine Abstracts

JOINT2145

Background: Sotos syndrome (SS) and Tatton-Brown-Rahman syndrome (TBRS) are two overgrowth syndromes characterized by distinct somatic features and intellectual disability. SS is caused by a heterozygous pathogenic variant in the NSD1 gene, while TBRS is caused by a heterozygous pathogenic variant in the DNMT3A gene.

Case: A 5-year-old patient presented to our hospital with vomiting and unsteadiness of gait. Imaging revealed a neoplasm occupying the third and fourth ventricles of the brain. Histological analysis confirmed the diagnosis of medulloblastoma. On clinical examination, the patient exhibited a height greater than 5 standard deviations (SD) above the mean and a weight greater than 2.5 SD according to the WHO 2006 growth charts. Somatic features were consistent with those seen in SS. Suspecting an overgrowth syndrome, genetic analysis was conducted using exome sequencing (Next Generation Sequencing). This revealed a pathogenic heterozygous variant in the NSD1 gene (c.6455G>A, p.(Arg2152Gln)) and a pathogenic heterozygous variant in the DNMT3A gene (c.2644C>T, p.(Arg882Cys)). Genetic testing of the parents revealed no similar variants, leading to a diagnosis of de novo SS and TBRS.

Conclusion: We present the first case of a patient diagnosed with both SS and TBRS, both arising de novo, in association with medulloblastoma. SS occurs in approximately 1 in 14,000 live births, while TBRS has an incidence of <1 in 1,000,000. Both SS and TBRS are typically transmitted in an autosomal dominant manner, with de novo mutations being the most common cause. Interestingly, the patient’s parents are first cousins (with first cousin paternal grandparents), which is known to increase the risk of inherited diseases. However, this patient developed two separate de novo mutations. Both SS and TBRS are associated with an increased risk of neoplasia, particularly within the hematopoietic system. To our knowledge, this is the first case of medulloblastoma reported in a patient with SS, although a previous case of TBRS with medulloblastoma has been described. This case emphasizes the importance of thorough genetic investigation when encountering a patient with an overgrowth syndrome, as clinical features alone may not provide an unambiguous diagnosis. Additionally, while rare, solid tumors should not be overlooked in these patients, and a careful assessment for tumor-related signs and symptoms is crucial.