DOOR syndrome

The DOOR syndrome is a very rare genetic disease that is most likely autosomal recessive. The abbreviation DOOR stands for the main symptoms Deafness ( deafness ), Osteodystrophy ( Knochendystrophie / malformation of the bones), Onychdystrophy ( nail dystrophy / developmental disorder of the nails ) and mental retardation ( mental retardation / developmental delay ). Another symptom is seizures. Worldwide less than 50 cases are known. The first description was in 1970 by the French geneticist R. Walbaum ( 1929-1985 ), although the term was first coined in 1975 by DOOR Cantwell.

Symptoms

In addition to the names leading symptoms, in varying degrees, additional, optional features are in the course of other publications have been described, eg:

• Polyhydramnios ( on average increased amniotic fluid during pregnancy) and increased nuchal fold during pregnancy
• Specific features, such as a big nose
• Severity and in some cases, treatment-resistant seizures, detectable by MRI of the brain organic changes
• Elevated levels of 2- oxoglutarate in blood and urine - this acid plays a role in the citric acid cycle
• Finger-like thumb
• Visual impairment
• Peripheral neuropathy (impaired nerve conduction of the extremities, starting to the brain ) and analgesia ( insensitivity to pain)

In all known cases in the medical literature there is a mental retardation, each with varying degrees of severity. The prognosis of life expectancy also varies considerably from toddler to adulthood.

Since there are in a majority of patients seizures, is partly from the DOOR (S ) syndrome spoken ( the S stands for Seizure ( convulsion) ).

Cause

The fact that the DOOR syndrome often occurs in siblings and blood relatives, suggests that it is an autosomal recessive genetic disorder, which probably has a metabolic background: in studies of interested parties were recently increased 2- oxoglutarate - detected values ​​in urine and plasma with reduced activity of 2- oxoglutarate dehydrogenase, which plays a key role in energy metabolism and biosynthesis. The exact cause of the DOOR syndrome, however, is not yet known.

Similar diseases

Feinmesser and Zelig described in 1961 also probably autosomal recessive syndrome characterized by deafness and onychodystrophy, Goodman et al describes in his syndrome with similar symptoms an autosomal dominant pattern of inheritance. However, both forms are syndrome without mental retardation. Nevin has this heterogeneous syndrome group published together in 1982 in a Overview.