Hypochrondroplasia is a genetic disorder characterized by small stature and disproportionately short arms, legs, hands, and feet (short-limbed dwarfism). Short stature often is not recognized until early to mid childhood or, in some cases, as late as adulthood. In those with the disorder, bowing of the legs typically develops during early childhood but often improves spontaneously with age. Some affected individuals may also have an abnormally large head (macrocephaly), a relatively prominent forehead, and/or other physical abnormalities associated with the disorder. In addition, in about 10 percent of cases, mild mental retardation may be present.
In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history. In other instances, the disorder is familial with autosomal dominant inheritance.
Hypochondroplasia is primarily characterized by small stature, disproportionately short arms and legs (limbs), mild to moderate shortness of the fingers and toes (brachydactyly), and broad, short hands and feet (i.e., short-limbed dwarfism). Slow growth often is not apparent at birth; as noted above, it may not be recognized until about two to three years of age, later during childhood, or as late as adulthood.
In those with hypochondroplasia, shortening of the limbs may be relatively mild or moderate. During early childhood, outward bowing of the legs (i.e., bowlegs [genu varum]) typically appears that is pronounced during weight bearing. This condition often improves spontaneously later during childhood. Many affected individuals also have limited extension and rotation of the elbows. In addition, beginning in childhood, exercise may result in minor aching or discomfort of the elbows, knees, and/or ankles. In affected adults, such joint pain may extend to involve the lower back. Approximately one third may also have abnormally pronounced inward curvature of the spine of the lower back (lordosis).
Some individuals with hypochondroplasia also have an abnormally large head (macrocephaly). In addition, the skull may be relatively broad and short (brachycephaly) or rectangular in shape with a slightly prominent forehead. However, the facial appearance is typically normal. Reports indicate that mild mental retardation may also be present in approximately 10 percent of affected individuals.
In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history of the disorder. According to researchers, such cases typically represent new (sporadic) genetic changes (mutations) that may be transmitted as an autosomal dominant trait (i.e., new dominant gene mutations). Investigators have noted increased age of the father (advanced paternal age) in some instances of apparently sporadic hypochondroplasia.
Familial cases of the disorder have also been reported. In such instances, the disorder has autosomal dominant inheritance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) may be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
Researchers indicate that hypochondroplasia often appears to result from specific mutations of a gene known as “fibroblast growth factor receptor-3” (FGFR3). The FGFR3 gene is located on the short arm (p) of chromosome 4 (4p16.3). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. Therefore, chromosome 4p16.3 refers to band 16.3 on the short arm of chromosome 4.
Researchers also have found that different mutations of the same gene (i.e., FGFR3) may cause achondroplasia, indicating that hypochondroplasia and achondroplasia are allelic disorders. (An allele is one of two or more alternative forms of a gene that may occupy a particular chromosomal location.) Achondroplasia is a more severe form of short-limbed dwarfism that may be characterized by certain features similar to those seen in hypochondroplasia. (For further information, please see the “Related Disorders” section of this report below.)
Genetic analysis has revealed that some individuals with hypochondroplasia do not have currently identified mutations of the FGFR3 gene. In such cases, researchers suggest that the disorder may result from mutations of different disease genes (genetic heterogeneity) or, possibly, from other, currently undetected FGFR3 gene mutations. Further research is necessary to learn more about the underlying genetic causes of hypochondroplasia.
Hypochondroplasia appears to affect females and males in relatively equal numbers. The features of the disorder were originally reported in 1913; hypochondroplasia was described as a distinct disease entity in 1924. Over 100 cases have since been recorded in the medical literature, including isolated (sporadic) and familial cases. Hypochondroplasia is thought to have an incidence of approximately one-twelfth that of achondroplasia. (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.) The estimated frequency of achondroplasia has ranged from about one in 15,000 to one in 35,000 births. (For further information on achondroplasia, please see the “Related Disorders” section of this report below.)
As noted previously, in individuals with hypochondroplasia, short stature often may not be recognized until early or mid childhood or as late as adulthood. The disorder may be diagnosed based upon thorough clinical examination; identification of characteristic physical findings (e.g., short stature, brachydactyly, genu varum, macrocephaly); x-ray studies; and/or other diagnostic techniques.
The treatment of hypochondroplasia is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians or internists; physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); surgeons; physical therapists; and/or other health care professionals.
Various orthopedic techniques, including surgery, may be recommended to help treat or correct certain skeletal abnormalities associated with the disorder. For example, as noted above, although outward bowing of the legs tends to improve during later childhood, surgical straightening may be advised in some cases.
In women with hypochondroplasia who are pregnant, Cesarean section is often necessary for delivery.
Early intervention may be important to help ensure that affected children reach their potential. Special services that may be beneficial may include special education, physical therapy, occupational therapy, and/or other medical, social, or vocational services.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Jones KL. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:346-53.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:171-76.
Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:11-12, 918-19.
Ramaswami U, et al. Genotype and phenotype in hypochondroplasia. J Pediatr. 1998;133:99-102.
Rousseau F, et al. Clinical and genetic heterogeneity of hypochondroplasia. J Med Genet. 1996;33:749-52.
Bellus GA, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995;10:357-59.
Stoilov I, et al. A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia. Am J Med Genet. 1995;55:127-33.
Wynne-Davies R, et al. Achondroplasia and hypochondroplasia. Clinical variation and spinal stenosis. J Bone Joint Surg (Br). 1981;63B:508-15.
Newman DE, et al. Hypochondroplasia. J Can Assoc Radiol. 1975;26:95-103.
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 146000; 1/11/01. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?146000.
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 100800; 2/6/01. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?100800.
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