DOOR syndrome is a rare multisystem genetic disorder, consisting of deafness (sensorineural), onychodystrophy, osteodystrophy, and mental retardation. Seizures reported frequently in this condition are often refractory to treatment.

Key words: Deafness, DOOR syndrome, Onychodystrophy, Osteodystrophy, Mental retardation.

A 14-month-old boy presented with history of focal clonic seizures since the age of 5 months. The boy was the only child of a consanguineous marriage, born full term by normal vaginal delivery. There was no history of polyhydramnios. His birthweight was 3.5 kg and there were no perinatal or neonatal problems. Developmental retardation maximally affected the motor and language milestones while cognitive and social milestones were minimally delayed . He had no response to verbal or nonverbal sounds. Family history was unremarkable.

On examination, he weighed 6.04 kg (<5th centile), length was 65.5 cm (<5th centile), and head circumference 43.5 cm (<5th centile). There were no distinctive facial features. Dentition was normal. General examination showed characteristic abnormalities of the digits including abnormal thumbs, which were unusually long and had an extra flexion crease bilaterally. Hypoplastic nails with clinodactyly was seen bilaterally on the fifth finger and small deep-set nails were present on all other digits. Similarly, nails were absent in the 2nd through 4th toes, while the 1st and 5th toes had hypoplastic nails bilaterally (Fig 1). Systemic examination including neurologic examination was normal except for deafness. Ophthalmic examination was also normal.

Fig. 1 Absent nails in 2nd through 4th toes and hypoplastic nails in fifth toe.	Fig. 2 Triphalangeal thumb and hypoplastic distal phalanx in other fingers.

Investigations revealed profound bilateral sensorineural deafness on BAER test. Biochemical workup was within normal limits. Urinary 2-oxoglutaric acid was elevated. Interictal EEG, CSF study and MRI brain, and echocardiogram all were normal. USG abdomen did not show any renal abnormalities. X-Ray of wrists and hands showed triphalangeal thumb on both sides with hypoplastic and dysplastic middle and distal phalanx. Distal phalanges of little fingers on both sides were aplastic (Fig 2). The seizures could only be controlled on a combination of valproate and topiramate.

Characteristic hand and nail malformations, with sensorineural deafness confirmed on BAER, and retardation suggested the diagnosis on clinical grounds. Due to paucity of cases and heterogeneity of the characteristic manifestations in DOOR syndrome, a tentative classification was proposed in 2000 [2] based on presence or absence of 2, oxoglutaric aciduria. The syndrome was divided into types I and II, with type I (elevated urinary 2-oxoglutaric acid) following a progressive neurologic course and early mortality and type II having a milder clinical course. Sensorineural deafness, onychodystrophy, osteodystrophy and develop-mental delay were reported in all published cases. Other features described are craniofacial abnormalities, especially coarse facies (78%). Only 67% reported abnormal findings in neuroimaging studies. Peripheral neuropathy and defects in other systems like cardiac (17%), renal (17%) and ophthalmic (29%) have also been reported [3]. Our patient did not have any of these additional features. Radiological evidence of distal phalangeal hypoplasia in toes and fingers and triphalangeal thumbs were the diagnostic features found in all reported cases. Seizure disorders from infancy are reported (87%) as a prominent clinical manifestation [3]. Seizures described are generalized tonic clonic, myoclonic, suspected absence and partial [4-6]. Seizures begin within the first year of life, may have a progressive nature and for the most part they are poorly controlled with medications [7-9]. Episodes of status epilepticus are common. Descriptions of EEG findings in published cases are variable but commonly show high amplitude slow activity and spike/sharp waves.

Prognostic markers have not been clearly defined. 32% have been documented to have early mortality, before 2 years of age with status epilepticus as the most common cause of death. After 4 years, deaths due to this syndrome have not been reported and the mortality is reported to be the same as that of general poulation. The differential diagnosis includes Coffin Siris syndrome (no deafness), Zimmerman Laband syndrome (hepato-splenomegaly present but mental retardation and deafness are not universal), fetal hydantoin syndrome, and fetal alcohol syndrome [3].

Acknowledgment: Dr IC Verma and Dr Seema Thakur, Gangaram Hospital, New Delhi.

Contributors: All authors contributed to diagnosis, and management of the case, and writing the manuscript.

Funding: None.

Competing interests: None stated.

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