DOOR syndrome

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Classification according to ICD-10
Q87.8 DOOR syndrome
ICD-10 online (WHO version 2019)

The DOOR syndrome is a very rare genetic disease that most likely autosomal inherited -rezessiv. The abbreviation stands for the DOOR main symptoms D eafness (Deafness), O steodystrophy (Knochendystrophie / malformation of bones), O nychodystrophy ( nail dystrophy / nail hypoplasia = developmental disorder of nails) and mental R etardation (Mental Retardation / Developmental delay). Another symptom is epileptic seizures. Fewer than 50 cases are known worldwide. It was first described in 1970 by the French geneticist R. Walbaum (1929–1985), although the term DOOR was first coined in 1975 by Ronald Cantwell .

Symptoms

In addition to the symptoms leading to the name, in varying degrees, additional, optional features have been described in the course of further publications, e.g. B .:

  • Polyhydramnios (above-average increase in amniotic fluid during pregnancy) and an increased neck fold during pregnancy
  • Specific facial features, such as a large nose
  • Severe and in some cases treatment-resistant seizures , organic changes detectable on brain MRI
  • Elevated levels of 2-oxoglutaric acid in blood and urine - this acid plays a role in the citric acid cycle
  • Finger-like thumb
  • Visual impairment
  • Peripheral neuropathy (disturbed nerve conduction from the extremities to the brain) and analgesia (insensitivity to pain)

In all cases known in the medical literature, there is an intellectual disability, each with a different degree of severity. The prognosis of life expectancy also varies greatly from toddler to adulthood.

Since epileptic seizures occur in the majority of patients, the DOOR (S) syndrome is also sometimes used (the S stands for S eizure (attack)).

root cause

The fact that DOOR syndrome often occurs in siblings and blood relatives suggests that it is an autosomal recessive genetic disorder that probably has a metabolic background: in recent studies of those affected, elevated levels of 2-oxoglutaric acid have been found. Values ​​in urine and plasma demonstrated with reduced activity of 2-oxoglutaric acid dehydrogenase, which plays a key role in energy metabolism and biosynthesis. The exact cause of the DOOR syndrome is not yet known.

Similar diseases

In 1961, Feinmesser and Zelig described a probably autosomal recessive syndrome with deafness and onychodystrophy, Goodman et alii described an autosomal dominant inheritance in their syndrome with similar symptoms. Both types of syndrome, however, are without intellectual disabilities. Nevin published a summary of this heterogeneous group of syndromes in 1982.

The Digito-reno-cerebral syndrome may be identical to the DOOR-Snydrom.

The DDOD syndrome is clinically similar, but inherited in an autosomal dominant manner .

Web links

Individual evidence

  1. ^ R. Walbaum, G. Fontaine, J. Lienhardt, JJ Piquet: Surdité familiale avec ostéo-onycho-dysplasie . In: J Génét hum . tape 18 , 1970, pp. 101-108 , PMID 5516283 .
  2. ↑ Ronald J. Cantwell: Congenital Sensori-Neural Deafness Associated with Onycho-Osteo Dystrophy and Mental Retardation (DOOR Syndrome) . In: Human Genetics . tape 26 , 1975, p. 261-265 . doi : 10.1007 / BF00281463 (currently unavailable)
  3. ↑ Feng Qi, Ranjan K Pradhan, Ranjan K Dash, Daniel A Beard: Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase . In: BMC Biochem . 2007, doi : 10.1186 / 1471-2091-12-53 , PMC 3195097 (free full text).
  4. ↑ Campeau PM, Kasperaviciute D, Lu JT, et al .: The genetic basis of DOORS syndrome: an exome-sequencing study. In: Lancet Neurol . tape 13 , 2014, p. 44-58 .
  5. ↑ S. Surendran, K. Michals-Matalon, S. Krywawych, QH Qazi, R. Tuchman, PL Rady, SK Tyring, R. Matalon: DOOR syndrome: deficiency of E1 component of the 2-oxoglutarate dehydrogenase complex . In: Am J Med Genet . tape 113 , no. 4 , 2002, p. 371-374 , PMID 12457410 .
  6. ^ AW James, SG Miranda, K. Culver, BD Hall, M. Golabi: DOOR syndrome: clinical report, literature review and discussion of natural history. In: Am J Med Genet . 143A, no. 23 , 2007, p. 2821-2831 , doi : 10.1002 / ajmg.a.32054 , PMID 17994565 .
  7. ↑ M. Feinmesser, S. Zelig: Congenital deafnes associated with onychodystrophy . In: Arch Otolaryng . tape 74 , 1961, pp. 507-508 , PMID 13892065 .
  8. ↑ RM Goodman, S. Lockareff, G. Gwinup: Hereditary congenital deafness with onychodystrophy . In: Arch Otolaryng . tape 90 , 1969, p. 474-477 , PMID 5806072 .
  9. ^ NC Nevin, PS Thomas, J. Calvert, MM Reid: Deafness, onycho-osteodystrophy, mental retardation (DOOR) syndrome . In: Am J Med Genet . tape 13 , 1982, pp. 325-332 , PMID 7180877 .