DOOR Syndrome

DOOR is an acronym standing for sensorineural deafness, onychodystrophy, osteodystrophy, microcephaly, and global developmental retardation. The disorder is characterized by sensorineural deafness, progressive blindness, onychodystrophy, triphalangeal thumbs, mental retardation, and seizures.

Approximately 20 cases have been reported in the literature.

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.

Unknown.

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, i.e., 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.

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.

Ensure that seizure control is optimized. Administer the patient's medication up to the morning of surgery. Check kidney function because urinary tract abnormalities are common in DOOR syndrome type I. If cardiac disease is suspected, an ECG and echocardiogram should be obtained.

In the presence of mental retardation, deafness, and progressive blindness, the patient coming to the unknown environment of the operating room may be anxious and agitated. Sedative and anxiolytic premedication and the presence of the primary caregiver during induction of anesthesia may be helpful. If the patient presents with micrognathia or retrognathia, airway management should be expected to be more challenging.

With anticonvulsive medication, the hepatic enzyme system may be induced and the metabolism of other drugs with predominantly hepatic elimination altered, requiring dose adjustment.

Eronen Syndrome: Genetic disorder characterized by severe digital, renal, and cerebral malformations.

Coffin-Siris Syndrome: Probably an autosomal dominant transmitted syndrome. Characteristics of the syndrome include developmental delay, hypoplasia of the fifth digit nails and phalanges, sparse scalp hair, bushy eyebrows, wide mouth, hirsutism, and prominent or hypertrophied lips.