Skeletal dysplasia

Gene: NFIX

Green List (high evidence)

Sotos syndrome-2 (SOTOS2) is clinically characterized by overgrowth, advanced bone age, macrocephaly, and dysmorphic facial features. Patients develop marfanoid habitus, with long and slender body, very low body mass, long narrow face, and arachnodactyly, with age. Impaired intellectual development and behavior anomalies are present.

Well established gene-disease association.

Marshall-Smith syndrome is allelic and characterised by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, ID, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia.

Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype (Malan syndrome). Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall-Smith syndrome.

Created: 6 Dec 2021, 7:25 a.m. | Last Modified: 6 Dec 2021, 7:25 a.m.

Panel Version: 0.10145

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Sotos syndrome 2 (MIM#614753); Marshall-Smith syndrome, MIM# 602535

Publications

• 33034087
• 29897170
• 30548146
• 25118028