DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome

Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):327-32. doi: 10.1002/ajmg.c.31412. Epub 2014 Aug 28.


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 novoSMARCB1 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.

Keywords: DOOR syndrome; DOORS syndrome; SMARCB1; TBC1D24; deafness; genotype-phenotype correlation; intellectual disability; phenotype; seizures.

Publication types

  • Comparative Study

MeSH terms

  • Abnormalities, Multiple / etiology*
  • Abnormalities, Multiple / genetics
  • Carrier Proteins / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Craniofacial Abnormalities / etiology*
  • Craniofacial Abnormalities / genetics
  • DNA-Binding Proteins / genetics
  • Exome
  • Face / abnormalities*
  • GTPase-Activating Proteins
  • Genetic Association Studies
  • Hand Deformities, Congenital / etiology*
  • Hand Deformities, Congenital / genetics
  • Hearing Loss, Sensorineural / etiology*
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Intellectual Disability / etiology*
  • Intellectual Disability / genetics
  • Membrane Proteins
  • Micrognathism / etiology*
  • Micrognathism / genetics
  • Mutation*
  • Nails, Malformed / etiology*
  • Nails, Malformed / genetics
  • Neck / abnormalities*
  • Nerve Tissue Proteins
  • SMARCB1 Protein
  • Seizures / genetics
  • Transcription Factors / genetics


  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • TBC1D24 protein, human
  • Transcription Factors

Supplementary concepts

  • Coffin-Siris syndrome
  • Digitorenocerebral Syndrome