:X-linked recessive chondrodysplasia punctata
{{Infobox medical condition (new)
| name = X-linked recessive chondrodysplasia punctata
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| field = Medical genetics
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X-linked recessive chondrodysplasia punctata is a type of chondrodysplasia punctata that can involve the skin, hair, and cause short stature with skeletal abnormalities, cataracts, and deafness.Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. {{ISBN|0-07-138076-0}}.{{rp|500}}
This condition is also known as arylsulfatase E deficiency, CDPX1, and X-linked recessive chondrodysplasia punctata 1. The syndrome rarely affects females, but they can be carriers of the recessive allele. Although the exact number of people diagnosed with CDPX1 is unknown, it was estimated that 1 in 500,000 have CDPX1 in varying severity.{{Cite journal|last1=Malou|first1=E.|last2=Gekas|first2=J.|last3=Troucelier-Lucas|first3=V.|last4=Mornet|first4=E.|last5=Razafimanantsoa|first5=L.|last6=Cuvelier|first6=B.|last7=Mathieu|first7=M.|last8=Thépot|first8=F.|date=2001-02-01|title=[X-linked recessive chondrodysplasia punctata. Cytogenetic study and role of molecular biology]|journal=Archives de Pédiatrie |volume=8|issue=2|pages=176–180|issn=0929-693X|pmid=11232459|doi=10.1016/S0929-693X(00)00181-0}} This condition is not linked to a specific ethnicity. The mutation that leads to a deficiency in arylsulfatase L (ARSL) occurs in the coding region of the gene. Absence of stippling, deposits of calcium, of bones and cartilage, shown on x-ray, does not rule out chondrodysplasia punctata or a normal chondrodysplasia punctata 1 (CDPX1) gene without mutation.{{Cite journal|last1=Casarin|first1=Alberto|last2=Rusalen|first2=Francesca|last3=Doimo|first3=Mara|last4=Trevisson|first4=Eva|last5=Carraro|first5=Silvia|last6=Clementi|first6=Maurizio|last7=Tenconi|first7=Romano|last8=Baraldi|first8=Eugenio|last9=Salviati|first9=Leonardo|date=2009-11-01|title=X-linked brachytelephalangic chondrodysplasia punctata: A simple trait that is not so simple|journal=American Journal of Medical Genetics Part A|language=en|volume=149A|issue=11|pages=2464–2468|doi=10.1002/ajmg.a.33039|issn=1552-4833|pmid=19839041|s2cid=9671515}} Stippling of the bones and cartilage is rarely seen after childhood. Phalangeal abnormalities are important clinical features to look for once the stippling is no longer visible.{{Cite journal|last=Maroteaux|first=P.|date=1989-05-01|title=Brachytelephalangic chondrodysplasia punctata: a possible X-linked recessive form|journal=Human Genetics|volume=82|issue=2|pages=167–170|issn=0340-6717|pmid=2722194|doi=10.1007/bf00284052|s2cid=23242273}} Other, more severe, clinical features include respiratory abnormalities, hearing loss, cervical spine abnormalities, delayed cognitive development, ophthalmologic abnormalities, cardiac abnormalities, gastroesophageal reflux, and feeding difficulties.{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1544/|title=GeneReviews|last1=Braverman|first1=Nancy E.|last2=Bober|first2=Michael|last3=Brunetti-Pierri|first3=Nicola|last4=Oswald|first4=Gretchen L.|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301713|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora J.H.|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Fong|editor-first8=Chin-To|editor-last9=Mefford|editor-first9=Heather C.|chapter=Chondrodysplasia Punctata 1, X-Linked}} CDPX1 actually has a spectrum of severity; different mutations within the CDPX1 gene have different effects on the catalytic activity of the ARSL protein. The mutations vary between missense, nonsense, insertions, and deletions.{{Cite journal|last1=Brunetti-Pierri|first1=Nicola|last2=Andreucci|first2=Maria Vittoria|last3=Tuzzi|first3=Rosaria|last4=Vega|first4=Giovanna Roberta|last5=Gray|first5=George|last6=McKeown|first6=Carol|last7=Ballabio|first7=Andrea|last8=Andria|first8=Generoso|last9=Meroni|first9=Germana|date=2003-03-01|title=X-linked recessive chondrodysplasia punctata: Spectrum of arylsulfatase E gene mutations and expanded clinical variability|journal=American Journal of Medical Genetics Part A|language=en|volume=117A|issue=2|pages=164–168|doi=10.1002/ajmg.a.10950|issn=1552-4833|pmid=12567415|s2cid=11888467|doi-access=free}}
Cause
The only known cause of this condition is a mutation in the X-linked chondrodysplasia punctata 1 (CDPX1) gene. Mutations in this gene result in a deficiency of arylsulfatase L.{{cite journal |vauthors=Nino M, Matos-Miranda C, Maeda M, etal |title=Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata |journal=Am. J. Med. Genet. A |volume=146A |issue=8 |pages=997–1008 |date=April 2008 |pmid=18348268 |doi=10.1002/ajmg.a.32159|s2cid=24869085 |doi-access=free }} Only 50-60% of cases have been shown to have mutations in this gene and the cause of the remaining cases is not yet known.{{citation needed|date=April 2017}}The CDPX1 gene is located on the short arm of the X chromosome (Xp22.3) on the Crick (minus) strand. It is 33,614 bases in length.{{cn|date=September 2021}}
File:Blausen 0435 GolgiApparatus.png
The mature protein has a molecular weight of 68 kilodaltons. It is glycosylated and is located in the Golgi apparatus. Its activity may be inhibited by warfarin.{{cite journal | vauthors = Franco B, Meroni G, Parenti G, Levilliers J, Bernard L, Gebbia M, Cox L, Maroteaux P, Sheffield L, Rappold GA, Andria G, Petit C, Ballabio A | year = 1995 | title = A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy | journal = Cell | volume = 81 | issue = 1| pages = 15–25 | doi=10.1016/0092-8674(95)90367-4 | pmid=7720070| doi-access = free }} It seems likely that warfarin induced embryotoxicity may be due at least in part to this inhibition.{{cn|date=September 2021}}
Brachytelephalangic chondrodysplasia punctata (BCDP) is the non-genetic, or environmentally produced, phenocopies associated with CDPX1. Causes of BCDP can also come from genetic effects, mainly due to mutations. Keutel syndrome, deficiency of vitamin K epoxide reductase subunit 1 (VKORC1), gamma-glutamyl carboxylase (GGCX), Xp contiguous deletion syndromes, and multiple sulfatase deficiency are all genetic conditions that are associated BCDP.
Diagnosis
This condition occurs almost exclusively in males. The mutation may be spontaneous or inherited from the mother. The typical clinical features are:{{cn|date=September 2021}}
- flat nasal tip
- short columella
- maxillary hypoplasia
- involvement of terminal phalanges
- stippled chondrodystrophy
=Biochemical confirmation=
The activity of arylsulfatase L can be measured with the substrate 4-methylumbelliferyl sulfate.{{citation needed|date=April 2017}}
Treatment
CDPX1 activity may be inhibited by warfarin because it is believed that ARSL has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.{{Cite journal|last=Maresz|title=Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health|journal=Integrative Medicine: A Clinician's Journal|year=2015|volume=14|issue=1|pages=34–9|pmid=26770129|pmc=4566462}}
See also
References
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External links
{{Medical resources
| DiseasesDB = 34567
| ICD10 = {{ICD10|Q|77|3|q|65}}
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| OMIM = 302950
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| GeneReviewsNBK = NBK1544
| GeneReviewsName = Chondrodysplasia Punctata 1, X-Linked Recessive
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