DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, Seizures) is characterized mainly by sensorineural deafness, shortened terminal phalanges with small nails of hands and feet, intellectual deficiency, and seizures. Half of the patients with all clinical features have mutations in TBC1D24. We review here the manifestations of patients clinically diagnosed with DOORS syndrome. In this cohort of 32 families (36 patients) we detected 13 individuals from 10 families with TBC1D24 mutations. Subsequent whole exome sequencing in the cohort showed the same de novo SMARCB1 mutation (c.1130G>A), known to cause Coffin-Siris syndrome, in two patients. Distinguishing features include retinal anomalies, Dandy-Walker malformation, scoliosis, rocker bottom feet, respiratory difficulties and absence of seizures, and 2-oxoglutaric aciduria in the patients with the SMARCB1 mutation. We briefly discuss the heterogeneity of the DOORS syndrome phenotype and the differential diagnosis of this condition.

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American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Erasmus MC: University Medical Center Rotterdam

Campeau, P.M, Hennekam, R.C.M, Aftimos, S, Banka, S, Begleiter, M.L, Bilo, L, … Sisodiya, S.M. (2014). DOORS syndrome: Phenotype, genotype and comparison with coffin-siris syndrome. American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 166(3), 327–332. doi:10.1002/ajmg.c.31412