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Further delineation of the DOOR syndrome
Insights
DOOR syndrome, a rare genetic disorder, presents with deafness, onychodystrophy, osteodystrophy, microcephaly, and developmental delays. Increased 2-oxoglutarate indicates a severe, often lethal, phenotype.
Area of Science:
- Genetics
- Metabolic Disorders
- Neurology
Background:
- DOOR syndrome is a rare genetic disorder.
- Characterized by a distinct set of physical and developmental anomalies.
Observation:
- Two related sibships exhibited features of DOOR syndrome.
- Clinical manifestations included deafness, onychodystrophy, osteodystrophy, microcephaly, global developmental retardation, and progressive blindness.
- Seizures with hypsarrhythmia were frequent and difficult to manage.
Findings:
- MRI revealed reduced myelination in one patient.
- Urine organic acid analysis showed a tenfold increase in 2-oxoglutarate.
- Placental cysts were observed in one case, a feature seen in other metabolic diseases.
Implications:
- Suggests potential genetic heterogeneity within DOOR syndrome.
- Elevated 2-oxoglutarate correlates with a severe, frequently lethal phenotype.
- Highlights the importance of metabolic investigations in DOOR syndrome diagnosis.
Abstract:
Two related sibships from an extended family have been observed with the features of the DOOR syndrome. These features included 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 brain scan of case 1 showed a number of abnormalities including markedly reduced myelination. The urine organic acid analysis showed a ten-fold increase of 2-oxoglutarate. In one patient the placenta was noted to have multiple fluid filled cysts, which is a feature reported in other metabolic diseases. It is suggested that there may be genetic heterogeneity in the syndrome, and the presence of increased 2-oxoglutarate is associated with a more severe phenotype which is frequently lethal.