Sotos Syndrome - NSD1

Klinische Symptomatik

Sotos syndrome (SoS) is a childhood overgrowth syndrome characterized by excessive pre- and postnatal growth, distinctive craniofacial features (macrocrania, coarse face with frontal bossing, highly arched palate, prognathism, pointed chin, large ears), large hands and feet, advanced bone age, and variable degrees of mental retardation, In addition, congenital heart defects, EEG changes, epileptic seizures, and possible susceptibility to tumors have been observed. Camptodactyly has been described.

Genetik

Recently, genetic defects of the NSD1 (nuclear receptor binding SET-Domain 1) gene on chromosome 5 (5q35) have been identified as the major cause of SoS, with intragenic mutations or submicroscopic microdeletions being found in about 60 to 75% of clinically diagnosed patients with SoS. Most reported cases of Sotos syndrome have been sporadic and may represent new dominant mutations, with deletions preferentially arising in the paternal germ line. Dominant intragenic NSD1 mutations have been also identified in a number of patients with weaver syndrome, and more recently in patients with Beckwith-Wiedeman syndrome (BWS). Conversely, a few SoS patients have recently been shown to be related to 11p15 anomalies, originally described as the molecular defect underlying BWS.

Häufigkeit

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Diagnostik