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The prevalence is unknown; about 50 cases have been reported to date.

Disease onset usually presents shortly after birth, but may present in infancy, with profound sensorineural deafness, small or absent nails, and short distal phalanges of hands and feet. About 1/4 of patients have long, finger-like thumbs. Facial features are highly variable and only a broad nasal bridge is present in 1/2 of all cases. Other facial signs, reported infrequently, include anteverted nares, long philtrum, thin upper vermilion and low set ears. Craniosynostosis has been reported in one patient. Optic atrophy leading to blindness, retinal detachment, strabismus, nystagmus, high myopia and cataracts are sometimes reported. Developmental delay is noted from infancy and can range from mild delays in early motor milestones to generalized and lifelong hypotonia. Seizures (often generalized tonic-clonic) are seen in most cases, usually begin in the first year of life and become more marked with age. Along with learning difficulties, behavioral problems may also be noted. Rare manifestations include dental (hypoplastic enamel, abnormal size of teeth), and internal organ (congenital heart defects, unilateral renal agenesis, cystic kidney, duplicated kidney) malformations. The disease is non-progressive.

DOORS (deafness-onychodystrophy-osteodystrophy-intellectual disability syndrome) syndrome is caused by mutations in the TBC1D24 gene (16p13.3) encoding a protein involved in the regulation of membrane trafficking. It seems likely that DOORS syndrome will prove to be a genetically heterogeneous disease and other causal genes will be identified in the future.

Patients are checked for each of the 5 major characteristics by conducting X-rays of the hands and feet, a brain stem auditory evoked response test for hearing loss, and an electroencephalogram (EEG). Elevated levels of 2-oxoglutaric acid in the urine and plasma have repeatedly been reported mostly in patients with TBC1D24 mutations. If present, DOORS syndrome is suspected, although elevated levels can also occur in other disorders. Molecular genetic testing identifying a TBC1D24 mutation may confirm the diagnosis but absence of the mutation does not mean a diagnosis of DOORS syndrome is incorrect.

Differential diagnoses include Coffin-Siris syndrome, intellectual disability-sparse hair-brachydactyly syndrome, Zimmermann-Laband syndrome, fetal alcohol syndrome and Temple-Baraitser syndrome, autosomal dominant deafness-onychodystrophy syndrome, and disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation.

Prenatal diagnosis is possible in families with a known disease-causing mutation.

DOORS syndrome is inherited autosomal recessively. If the clinical diagnosis has been established with a high degree of certainty, genetic counseling should be provided accordingly.

Treatment is supportive. Long-term management involves regular ophthalmologic and hearing tests as well as neurological exams such as EEGs. A feeding tube may be necessary in infants with feeding difficulties. Antiepileptic medication may be used to prevent or decrease the frequency of seizures but is not always effective.

Life expectancy is usually normal. Intellectual disability is lifelong but there is no known correlation between clinical manifestations and cognition. The number of known adults with DOORS syndrome is at present too small to predict the long term prognosis. Parkinsonism was reported in an adult.