X-linked chondrodysplasia punctata 1 is a disorder of cartilage and bone development that occurs almost exclusively in males. Chondrodysplasia punctata is an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In most infants with X-linked chondrodysplasia punctata 1, this stippling is seen in bones of the ankles, toes, and fingers; however, it can also appear in other bones. The stippling generally disappears in early childhood.

Other characteristic features of X-linked chondrodysplasia punctata 1 include short stature and unusually short fingertips and ends of the toes. This condition is also associated with distinctive facial features, particularly a flattened-appearing nose with crescent-shaped nostrils and a flat nasal bridge.

People with X-linked chondrodysplasia punctata 1 typically have normal intelligence and a normal life expectancy. However, some affected individuals have had serious or life-threatening complications including abnormal thickening (stenosis) of the cartilage that makes up the airways, which restricts breathing. Also, abnormalities of spinal bones in the neck can lead to pinching (compression) of the spinal cord, which can cause pain, numbness, and weakness. Other, less common features of X-linked chondrodysplasia punctata 1 include delayed development, hearing loss, vision abnormalities, and heart defects.

The prevalence of X-linked chondrodysplasia punctata 1 is unknown. Several dozen affected males have been reported in the scientific literature.

X-linked chondrodysplasia punctata 1 is caused by genetic changes involving the ARSL gene. This gene provides instructions for making an enzyme called arylsulfatase L. The function of this enzyme is unknown, although it appears to be important for normal skeletal development and is thought to participate in a chemical pathway involving vitamin K. Evidence suggests that vitamin K normally plays a role in bone growth and maintenance of bone density.

Between 60 and 75 percent of males with the characteristic features of X-linked chondrodysplasia punctata 1 have a mutation in the ARSL gene. These mutations reduce or eliminate the function of arylsulfatase L. Another 25 percent of affected males have a small deletion of genetic material from the region of the X chromosome that contains the ARSL gene. These individuals are missing the entire gene, so their cells produce no functional arylsulfatase L. Researchers are working to determine how a shortage of arylsulfatase L disrupts the development of bones and cartilage and leads to the characteristic features of X-linked chondrodysplasia punctata 1.

Some people with the features of X-linked chondrodysplasia punctata 1 do not have an identified mutation in the ARSE gene or a deletion involving the gene. Other, as-yet-unidentified genetic and environmental factors may also be involved in causing this disorder.

Genetic Testing Information

• Genetic Testing Registry: Chondrodysplasia punctata, brachytelephalangic, autosomal

Genetic and Rare Diseases Information Center

• Brachytelephalangic chondrodysplasia punctata

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• CHONDRODYSPLASIA PUNCTATA 1, X-LINKED RECESSIVE; CDPX1

Scientific Articles on PubMed

• PubMed

• Braverman NE, Bober MB, Brunetti-Pierri N, Suchy SF. Chondrodysplasia Punctata 1, X-Linked. 2008 Apr 22 [updated 2020 Oct 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1544/ Citation on PubMed
• Brunetti-Pierri N, Andreucci MV, Tuzzi R, Vega GR, Gray G, McKeown C, Ballabio A, Andria G, Meroni G, Parenti G. X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability. Am J Med Genet A. 2003 Mar 1;117A(2):164-8. doi: 10.1002/ajmg.a.10950. Citation on PubMed
• Casarin A, Rusalen F, Doimo M, Trevisson E, Carraro S, Clementi M, Tenconi R, Baraldi E, Salviati L. X-linked brachytelephalangic chondrodysplasia punctata: a simple trait that is not so simple. Am J Med Genet A. 2009 Nov;149A(11):2464-8. doi: 10.1002/ajmg.a.33039. Citation on PubMed
• Daniele A, Parenti G, d'Addio M, Andria G, Ballabio A, Meroni G. Biochemical characterization of arylsulfatase E and functional analysis of mutations found in patients with X-linked chondrodysplasia punctata. Am J Hum Genet. 1998 Mar;62(3):562-72. doi: 10.1086/301746. Citation on PubMed or Free article on PubMed Central
• Garnier A, Dauger S, Eurin D, Parisi I, Parenti G, Garel C, Delbecque K, Baumann C. Brachytelephalangic chondrodysplasia punctata with severe spinal cord compression: report of four new cases. Eur J Pediatr. 2007 Apr;166(4):327-31. doi: 10.1007/s00431-006-0239-4. Epub 2006 Aug 26. Citation on PubMed
• Maroteaux P. Brachytelephalangic chondrodysplasia punctata: a possible X-linked recessive form. Hum Genet. 1989 May;82(2):167-70. doi: 10.1007/BF00284052. Citation on PubMed
• Nino M, Matos-Miranda C, Maeda M, Chen L, Allanson J, Armour C, Greene C, Kamaluddeen M, Rita D, Medne L, Zackai E, Mansour S, Superti-Furga A, Lewanda A, Bober M, Rosenbaum K, Braverman N. Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata. Am J Med Genet A. 2008 Apr 15;146A(8):997-1008. doi: 10.1002/ajmg.a.32159. Citation on PubMed
• Sheffield LJ, Osborn AH, Hutchison WM, Sillence DO, Forrest SM, White SJ, Dahl HH. Segregation of mutations in arylsulphatase E and correlation with the clinical presentation of chondrodysplasia punctata. J Med Genet. 1998 Dec;35(12):1004-8. doi: 10.1136/jmg.35.12.1004. Citation on PubMed or Free article on PubMed Central