Overgrowth syndromes as described above
Sotos Syndrome - NSD1
Clinical Features
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.
Genetic Information
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.
Prevalence
1 : 10 000
Diagnostic
Indication
Method
High Resolution Melting and sequencing.
Deletions and/or duplications of one or more exons are captured by MLPA analysis.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
4 - 6 weeks