DOOR Syndrome

At a glance

DOOR is an acronym standing for sensorineural Deafness, Onychodystrophy, Osteodystrophy, microcephaly, and global developmental Retardation. This medical disorder is characterized by the presence of sensorineural deafness, craniofacial anomalies, progressive optic nerve blindness, peripheral polyneuropathy, onychodystrophy, triphalangeal thumbs, mental retardation, and seizures. Congenital cardiac defects are reported in 20% and consist of patent ductus arteriosus, atrial and ventricular septal defects. The majority of subjects have increased levels of 2-oxoglutarate in the plasma and urine.

Synonyms

Some authors have suggested that it may be the same as the Eronen Syndrome, however, since they are both very rare medical conditions, it remains difficult to make a determination. As this time, they are considered separate entities.

History

This medical condition was first described in 1961 by M. Feinmesser and eventually characterized by R. J. Cantwell in 1975.

Incidence

Approximately 50 cases have been reported in the literature.

Genetic inheritance

There are two forms of this syndrome, one being inherited autosomal dominantly (without mental retardation), the other inherited autosomal recessively. Parental consanguinity is a risk factor. Mutations in TBC1D24 have been identified in nine families.

Pathophysiology

Unknown.

Diagnosis

Diagnosis is mainly clinical. However, patients with the recessive type and a more severe phenotype, who are classified as DOOR Syndrome Type I (with early onset of seizures, ie, within the first 6 months of life, and a progressive course with blindness, deafness, and early death), show increased plasma and urinary concentrations of 2-oxoglutarate and its metabolite α-hydroxyglutarate. (2-Oxoglutarate, a precursor of glutamate, is involved in the regulation of gluconeogenesis in liver and kidney and of ammoniagenesis in the kidney.) DOOR Syndrome Type II is not associated with increased concentrations of organic acids and shows a less severe clinical course.

Clinical aspects

Main clinical characteristics of this syndrome are the presence of congenital sensorineural deafness, mental retardation, and onychoosteodystrophy, which consists of hypoplasia of the terminal phalanges, triphalangeal thumbs, dysplastic or absent fingernails and toenails, and pathologic (arch pattern) dermatoglyphics. Affected patients usually develop seizures early in life, which may be difficult to control and can cause death. Other, but less frequent, anomalies include microcephaly, plagiocephaly, low-set ears, hypertelorism, broad nose with large nostrils, thin upper lip with long philtrum, micrognathia, retrognathia, and high arched palate. Cardiac defects and urinary tract anomalies have been described. Mental retardation is not a feature of the autosomal dominant transmitted form of the DOOR Syndrome.

Precautions before anesthesia

Ensure that seizure control is optimized. Administer the patient’s medication up to the morning of surgery. Check kidney function because urinary tract ...