Mandibuloacral dysplasia
| Classification according to ICD-10 | |
|---|---|
| Q87.5 | Other congenital malformation syndromes with other skeletal changes |
| ICD-10 online (WHO version 2019) | |
The mandibulo-acral dysplasia ( MAD ) is a very rare congenital disease with the main features of the later closing Fontanelle , facial abnormalities, hypoplasia of the mandible and clavicles and spotty skin pigmentation .
Synonyms are: restrictive dermopathy; Craniomandibular dermatodysostosis
The first description was in 1971 by LW Young and colleagues.
The delimitation as an independent clinical picture was carried out by O. Welsh in 1975.
distribution
The frequency is given as less than 1 in 1,000,000, inheritance is autosomal - recessive .
Classification and cause
Depending on the clinical extent of lipatrophy, two forms are distinguished:
- MADA with type A-lipodystrophy, mainly concerning the limbs, with homozygous missense mutations in LMNA- gene (Arg527His and Ala529Val) at the locus 1q21.2, which for the core structural proteins Lamin A / C coded.
- MADB with type B lipodystrophy affecting the whole body and mutations in the ZMPSTE24 gene at locus 1p34, which codes for a zinc endoprotease which is required for the lamin A / C protein.
Other diseases with mutations in the LMNA gene are: partial lipatrophy, Emery Dreifuss muscular dystrophy , limb girdle dystrophy LGMD1B , non-obstructive cardiomyopathy (CMD 1A), Charcot-Marie-Tooth disease and Hutchinson-Gilford syndrome .
Clinical manifestations
Clinical criteria are:
- Late closing of the fontanel
- Facial abnormalities such as wide cranial sutures , cranial bones , bald head , prominent head veins, bird head face, pseudo- exophthalmos
- Abnormal tooth positions
- Growth retardation starting from the age of 6
- Sclerosis of the skin, hyperpigmentation in the neck
- Hypoplasia of the mandible and collarbones
- bell-shaped deformation of the chest
- Acroosteolysis from the age of 2 on hands and feet
- Dystrophy of the fingernails and toenails
- prominent interphalangeal joints
Sometimes there are also signs of progeria as well as a diffuse change in the connective tissue and the vascular walls
Differential diagnosis
The Werner Syndrome , Hutchinson-Gilford Syndrome , Kleidocranial Dysplasia , Acrogeria , Crane-Heise Syndrome and Yunis-Varon Syndrome are to be distinguished .
therapy
Treatment is directed against insulin resistance . Leptin can potentially affect lipatrophy.
literature
- JC Hoeffel, L. Mainard, P. Chastagner, CC Hoeffel: Mandibulo-acral dysplasia. In: Skeletal radiology. Vol. 29, No. 11, November 2000, pp. 668-671, PMID 11201039 .
Individual evidence
- ↑ a b c d e Mandibuloacral Dysplasia. In: Orphanet (Rare Disease Database).
- ↑ a b Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
- ↑ LW Young, JF Radebaugh, P. Rubin, JA Sensenbrenner, G. Fiorelli, VA McKusick: New syndrome manifested by mandibular hypoplasia, acroosteolysis, stiff joints and cutaneous atrophy (mandibuloacral dysplasia) in two unrelated boys. In: Birth defects original article series. Vol. 7, No. 7, June 1971, pp. 291-297, PMID 5173234 .
- ^ O. Welsh: Study of a family with a new progeroid syndrome. In: Birth defects original article series. Vol. 11, No. 5, 1975, pp. 25-38, PMID 1240776 .
- ↑ MADA. In: Online Mendelian Inheritance in Man . (English)
- ↑ Dysplasia, mandibulo-acral, with type A lipodystrophy. In: Orphanet (Rare Disease Database).
- ↑ MADB. In: Online Mendelian Inheritance in Man . (English)
- ↑ Dysplasia, mandibulo-acral, with type B lipodystrophy. In: Orphanet (Rare Disease Database).
