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X-linked chondrodysplasia punctata 2

Reviewed November 2011

What is X-linked chondrodysplasia punctata 2?

X-linked chondrodysplasia punctata 2 is a disorder characterized by bone, skin, and eye abnormalities. It occurs almost exclusively in females.

Although the signs and symptoms of this condition vary widely, almost all affected individuals have chondrodysplasia punctata, an abnormality that appears on x-rays as spots (stippling) near the ends of bones and in cartilage. In this form of chondrodysplasia punctata, the stippling typically affects the long bones in the arms and legs, the ribs, the spinal bones (vertebrae), and the cartilage that makes up the windpipe (trachea). The stippling is apparent in infancy but disappears in early childhood. Other skeletal abnormalities seen in people with X-linked chondrodysplasia punctata 2 include shortening of the bones in the upper arms and thighs (rhizomelia) that is often different on the right and left sides, and progressive abnormal curvature of the spine (kyphoscoliosis). As a result of these abnormalities, people with this condition tend to have short stature.

Infants with X-linked chondrodysplasia punctata 2 are born with dry, scaly patches of skin (ichthyosis) in a linear or spiral (whorled) pattern. The scaly patches fade over time, leaving abnormally colored blotches of skin without hair (follicular atrophoderma). Most affected individuals also have sparse, coarse hair on their scalps.

Most people with X-linked chondrodysplasia punctata 2 have clouding of the lens of the eye (cataracts) from birth or early childhood. Other eye abnormalities that have been associated with this disorder include unusually small eyes (microphthalmia) and small corneas (microcornea). The cornea is the clear front surface of the eye. These eye abnormalities can impair vision.

In affected females, X-linked chondrodysplasia punctata 2 is typically associated with normal intelligence and a normal lifespan. However, a much more severe form of the condition has been reported in a small number of males. Affected males have some of the same features as affected females, as well as weak muscle tone (hypotonia), changes in the structure of the brain, moderately to profoundly delayed development, seizures, distinctive facial features, and other birth defects. The health problems associated with X-linked chondrodysplasia punctata 2 are often life-threatening in males.

How common is X-linked chondrodysplasia punctata 2?

X-linked chondrodysplasia punctata 2 has been estimated to affect fewer than 1 in 400,000 newborns. However, the disorder may actually be more common than this estimate because it is likely underdiagnosed, particularly in females with mild signs and symptoms.

More than 95 percent of cases of X-linked chondrodysplasia punctata 2 occur in females. About a dozen males with the condition have been reported in the scientific literature.

What genes are related to X-linked chondrodysplasia punctata 2?

X-linked chondrodysplasia punctata 2 is caused by mutations in the EBP gene. This gene provides instructions for making an enzyme called 3β-hydroxysteroid-Δ8,Δ7-isomerase, which is responsible for one of the final steps in the production of cholesterol. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals (particularly egg yolks, meat, poultry, fish, and dairy products). Although too much cholesterol is a risk factor for heart disease, this molecule is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and plays a role in the production of certain hormones and digestive acids.

Mutations in the EBP gene reduce the activity of 3β-hydroxysteroid-Δ8,Δ7-isomerase, preventing cells from producing enough cholesterol. A shortage of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the body. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of X-linked chondrodysplasia punctata 2.

Related Gene(s)

Changes in this gene are associated with X-linked chondrodysplasia punctata 2.

  • EBP

How do people inherit X-linked chondrodysplasia punctata 2?

This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the EBP gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of 3β-hydroxysteroid-Δ8,Δ7-isomerase and other cells produce none. The resulting overall reduction in the amount of this enzyme underlies the signs and symptoms of X-linked chondrodysplasia punctata 2.

In males (who have only one X chromosome), a mutation in the EBP gene can result in a total loss of 3β-hydroxysteroid-Δ8,Δ7-isomerase. A complete lack of this enzyme is usually lethal in the early stages of development, so few males have been born with X-linked chondrodysplasia punctata 2.

Where can I find information about diagnosis or management of X-linked chondrodysplasia punctata 2?

These resources address the diagnosis or management of X-linked chondrodysplasia punctata 2 and may include treatment providers.

  • Gene Review: Chondrodysplasia Punctata 2, X-Linked (http://www.ncbi.nlm.nih.gov/books/NBK55062)
  • Genetic Testing Registry: Chondrodysplasia punctata 2 X-linked dominant (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0282102)

You might also find information on the diagnosis or management of X-linked chondrodysplasia punctata 2 in Educational resources (http://www.ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/x-linked-chondrodysplasia-punctata-2/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about X-linked chondrodysplasia punctata 2?

You may find the following resources about X-linked chondrodysplasia punctata 2 helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for X-linked chondrodysplasia punctata 2?

  • CDPX2
  • chondrodysplasia punctata 2, X-linked
  • Conradi-Hünermann-Happle syndrome
  • Conradi-Hünermann Syndrome
  • Happle syndrome
  • X-linked dominant chondrodysplasia punctata

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked chondrodysplasia punctata 2?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding X-linked chondrodysplasia punctata 2?

acids ; cartilage ; cell ; cholesterol ; chromosome ; cornea ; digestive ; egg ; embryonic ; enzyme ; gene ; hypotonia ; ichthyosis ; inherited ; kyphoscoliosis ; molecule ; muscle tone ; mutation ; sex chromosomes ; short stature ; stature ; syndrome ; toxic ; X-linked dominant ; x-rays

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Aughton DJ, Kelley RI, Metzenberg A, Pureza V, Pauli RM. X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene mosaicism in a male. Am J Med Genet A. 2003 Jan 30;116A(3):255-60. (http://www.ncbi.nlm.nih.gov/pubmed/12503102?dopt=Abstract)
  • Braverman N, Lin P, Moebius FF, Obie C, Moser A, Glossmann H, Wilcox WR, Rimoin DL, Smith M, Kratz L, Kelley RI, Valle D. Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase cause X-linked dominant Conradi-Hünermann syndrome. Nat Genet. 1999 Jul;22(3):291-4. (http://www.ncbi.nlm.nih.gov/pubmed/10391219?dopt=Abstract)
  • Derry JM, Gormally E, Means GD, Zhao W, Meindl A, Kelley RI, Boyd Y, Herman GE. Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. jderry@immunex.com. Nat Genet. 1999 Jul;22(3):286-90. (http://www.ncbi.nlm.nih.gov/pubmed/10391218?dopt=Abstract)
  • Furtado LV, Bayrak-Toydemir P, Hulinsky B, Damjanovich K, Carey JC, Rope AF. A novel X-linked multiple congenital anomaly syndrome associated with an EBP mutation. Am J Med Genet A. 2010 Nov;152A(11):2838-44. doi: 10.1002/ajmg.a.33674. (http://www.ncbi.nlm.nih.gov/pubmed/20949533?dopt=Abstract)
  • Gene Review: Chondrodysplasia Punctata 2, X-Linked (http://www.ncbi.nlm.nih.gov/books/NBK55062)
  • Herman GE, Kelley RI, Pureza V, Smith D, Kopacz K, Pitt J, Sutphen R, Sheffield LJ, Metzenberg AB. Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome). Genet Med. 2002 Nov-Dec;4(6):434-8. (http://www.ncbi.nlm.nih.gov/pubmed/12509714?dopt=Abstract)
  • Hoang MP, Carder KR, Pandya AG, Bennett MJ. Ichthyosis and keratotic follicular plugs containing dystrophic calcification in newborns: distinctive histopathologic features of x-linked dominant chondrodysplasia punctata (Conradi-Hünermann-Happle syndrome). Am J Dermatopathol. 2004 Feb;26(1):53-8. (http://www.ncbi.nlm.nih.gov/pubmed/14726822?dopt=Abstract)
  • Ikegawa S, Ohashi H, Ogata T, Honda A, Tsukahara M, Kubo T, Kimizuka M, Shimode M, Hasegawa T, Nishimura G, Nakamura Y. Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. Am J Med Genet. 2000 Oct 2;94(4):300-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11038443?dopt=Abstract)
  • Milunsky JM, Maher TA, Metzenberg AB. Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP. Am J Med Genet A. 2003 Jan 30;116A(3):249-54. (http://www.ncbi.nlm.nih.gov/pubmed/12503101?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2011
Published: September 8, 2014