Parastremmatic dwarfism
| Parastremmatic dwarfism | |
|---|---|
| Other names | Parastremmatic dysplasia[1] |
 | |
| Parastremmatic dwarfism has an autosomal dominant pattern of inheritance | |
Parastremmatic dwarfismis a rarebone diseasethat features severedwarfism,thoracickyphosis(a type ofscoliosisthat affects the upper back), a distortion and twisting of the limbs,contracturesof the large joints, malformations of thevertebraeandpelvis,andincontinence.The disease was first reported in 1970 by Leonard Langer and associates; they used the termparastremmaticfrom the Greekparastremma,ordistorted limbs,to describe it. OnX-rays,the disease is distinguished by a "flocky" or lace-like appearance to the bones.[2]The disease iscongenital,which means it is apparent at birth. It is caused by amutationin theTRPV4gene, located onchromosome 12in humans. The disease is inherited in anautosomaldominantmanner.[2][3][4]
Presentation
[edit]Parastremmatic dwarfism is apparent at birth, with affected infants usually being described as "stiff", or as "twisted dwarfs" when the skeletal deformities and appearance of dwarfism further present themselves. Skeletal deformities usually develop in the sixth to twelfth month of an infant's life. The deformities may be attributed toosteomalacia,a lack ofbone mineralization.[citation needed]
Parastremmatic Dwarfism is further characterised by short stature, bowing of extremeties and further neuroskeletal dysplasia.[citation needed]
Genetics
[edit]
Parastremmatic dwarfism is caused by amissense mutation(where oneamino acidis replaced by another in agene sequence) in theTRPV4gene,[4]locatedon the long arm of humanchromosome12,at 12q24.11.[5]The mutation is inexon11 of the gene, and is labelled R594H; this means that thecodon(the code for an amino acid molecule) forargininewas erroneously substituted by a codon forhistidineat position 594 in that exon. This same mutation in theTRVP4gene is known to cause theKozlowski typeofspondylometaphyseal dysplasia.[4][6]
Parastremmatic dwarfism is inherited in an autosomal dominant manner,[7]which means that the defective gene responsible for the disease is located on anautosome(chromosome 12 is an autosome), and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who also has the disorder.[2]
Parastremmatic Dwarfism results from mutations within the N-ankyrin domain of TRPV4, which has been identified to be involved in regulation of the TRPV4 calcium ion channel. This influx of calcium may be responsible for neuronal cell death, as well as affecting levels of circulating growth hormones.[citation needed]
Parastremmatic Dwarfism is a very rare disorder, and as of 2011, only 5 people were diagnosed worldwide. As such, functional analysis has proved elusive at this time.[citation needed]
Diagnosis
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Treatment
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References
[edit]- ^"Parastremmatic dwarfism | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program".rarediseases.info.nih.gov.Retrieved27 October2019.
- ^abcHoran, F.; Beighton, P. (Aug 1976)."Parastremmatic dwarfism".The Journal of Bone and Joint Surgery. British Volume.58(3): 343–346.doi:10.1302/0301-620X.58B3.956253.PMID956253.
- ^Langer, L. O.; Petersen, D.; Spranger, J. (Nov 1970). "An unusual bone dysplasia: Parastremmatic dwarfism".The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine.110(3): 550–560.doi:10.2214/ajr.110.3.550.PMID4992387.
- ^abcNishimura, G.; Dai, J.; Lausch, E.; Unger, S.; Megarbané, A.; Kitoh, H.; Kim, O. H.; Cho, T. J.; Bedeschi, F.; Benedicenti, F.; Mendoza-Londono, R.; Silengo, M.; Schmidt-Rimpler, M.; Spranger, J.; Zabel, B.; Ikegawa, S.; Superti-Furga, A. (Jun 2010)."Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations"(PDF).American Journal of Medical Genetics Part A.152A(6): 1443–1449.doi:10.1002/ajmg.a.33414.PMID20503319.S2CID40015069.Archived fromthe original(PDF)on 2018-07-21.Retrieved2019-09-19.
- ^Online Mendelian Inheritance in Man(OMIM):Parastremmatic dwarfism - 168400Retrieved 11-19-2011.
- ^Online Mendelian Inheritance in Man(OMIM):Transient Receptor Potential Cation Channel, Subfamily V, Member 4;TRPV4- 605427#0003Retrieved 11-19-2011.
- ^Canepa, G.; Maroteaux, P.; Pietrogrande, V. (2000).Dysmorphic Syndromes and Constitutional Disease of the Skeleton.PICCIN. pp. 1421–1424.ISBN8829915025.