Sotos Syndrome 2

A number sign (#) is used with this entry because Sotos syndrome-2 (SOTOS2) is caused by heterozygous mutation in the NFIX gene (164005) on chromosome 19p13.

Marshall-Smith syndrome (MRSHSS; 602535) is also caused by heterozygous mutation in the NFIX gene.

For a discussion of genetic heterogeneity of Sotos syndrome, see 117550.

Clinical Features

Malan et al. (2010) reported 3 unrelated patients with a similar phenotype consisting of postnatal overgrowth, macrocephaly, advanced bone age, long narrow face, high forehead, slender habitus, scoliosis, unusual behavior characterized especially by anxiety, and mental retardation. One of the patients had previously been diagnosed with a 'Sotos-like syndrome.'

Inheritance

Most reported cases of Sotos syndrome-2 have been sporadic and may represent new dominant mutations (Malan et al., 2010; Yoneda et al., 2012).

Cytogenetics

Malan et al. (2010) used a high-resolution array CGH in 18 patients with unexplained syndromic overgrowth and identified 2 patients with a de novo 19p13.1 monosomy. The deletions involved a single common gene, NFIX.

Molecular Genetics

In a patient who had previously been diagnosed with a 'Sotos-like syndrome,' Malan et al. (2010) identified a heterozygous de novo nonsense mutation (Q190X; 164005.0001) in the NFIX gene. RT-PCR analysis in patient fibroblasts indicated that the phenotype was due to NFIX haploinsufficiency. The phenotype in this patient was similar to 2 patients found by Malan et al. (2010) to have a de novo 19p13.1 monosomy involving a deletion in the NFIX gene.

In 2 Japanese patients diagnosed with Sotos syndrome who did not have mutations in the NSD1 gene (606681), Yoneda et al. (2012) identified different heterozygous splice site mutations (164005.0011-164005.0012). One mutation was de novo and the other was possibly inherited from the mother, who was not available for study. Both mutations were absent in 250 healthy Japanese controls.