DOOR Syndrome is an extremely rare, neurometabolic disorder with a progressive natural history. The name DOOR is an acronym for the four cardinal features of this condition, namely, deafness, onychodystrophy, osteodystrophy, and mild to severe mental retardation. The deafness is congenital and sensorineural and is due to malformations of the inner ear or auditory ear. Onychodystrophy or nail malformations include absent, hypoplastic or rudimentary nails, discoloration, and changes in the texture and shape of the finger and toe nails. Skeletal abnormalities are also concentrated at the hands and feet, and include triphalangy, and hypoplasia of digital bones. Mental retardation is associated with seizures, and peripheral polyneuropathy. Patients also have typical facial features, which include large nose, wide nasal bridge, prominent philtrum, arched palate, down-turned corners of the mouth, slight ptosis, convergent strabismus, and other ocular abnormalities. Till date, only about 40 cases of DOOR Syndrome have been reported worldwide. Diagnosis of DOOR Syndrome is made on the basis of the clinical features. The neurological manifestations of the condition have a progressive nature, and the disease, therefore, follows a deteriorative course.
DOOR syndrome is associated with mutations in TBC1D24 gene, which encodes a protein involved in neuronal projections development.
Rajab et al. (2000) reported four cases of DOOR syndrome in two related sibships from an extended Omani family. The children had deafness, onychodystrophy, osteodystrophy, microcephaly, and global developmental retardation with progressive blindness. Seizures, which were associated with hypsarrhythmia, were frequent and difficult to control and ultimately were the cause of death in two patients. An MRI of the brain in one patient showed a number of abnormalities including markedly reduced myelination. The urine organic acid analysis showed a 10-fold increase of 2-oxoglutarate. In one patient, the placenta was noted to have multiple fluid-filled cysts. Rajab et al. (2000) suggested that there may be genetic heterogeneity in the autosomal recessive form of this syndrome, and that the presence of increased 2-oxoglutarate is associated with a more severe phenotype, which is frequently lethal.