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1999-05-16-22 Achondroplasia © Jeanty www.thefetus.net/


Achondroplasia

Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Definition:  Rhizomelic micromelia associated with frontal bossing and low nasal bridge.

Synonyms: None.

Incidence: Common: 0.5-1.5:10,000

Etiology: Defective cartilaginous molding of the bone precursor.

Diagnosis: The micromelia is the most obvious finding with limbs shorter than the 5th percentile after 20 weeks. (fig 1) The frontal bossing and depressed nasal bridge can also be recognized (fig 2). Occasionally more subtle anomalies such as the trident hand (an increased interspace between the 3rd and 4th digit) or the lack of widening of the lumbar canal can also be identified (fig 3).

Genetic anomalies: Achondroplasia is an autosomal dominant skeletal dysplasia caused by mutation in the fibroblast growth factor receptor-3 gene which is located on the short arm of chromosome 4 at the 16.3 locus[1],[2]. Bellus has demonstrated that the anomaly was due to a glycine to arginine substitution at codon 380[3]. These papers are landmarks in our knowledge about skeletal dysplasias. Before these papers skeletal dysplasias were almost strictly classified by radiological criteria. These papers marked the beginning of an intense and successful search for gene mapping of skeletal dysplasia. Many of which where subsequently recognized to result from alterations of the Fibroblast Growth Factors (I-III).

Differential diagnosis: The differential diagnosis is with multiple condition such as:

·         Thanatophoric dysplasia (narrower chest, platyspondyly, more severe micromelia, no trident hand, more severe polyhydramnios)

·         Achondrogenesis (very poor mineralization – with lack of echogenicity of the bones --, more severe micromelia, more severe polyhydramnios)

·         Osteogenesis imperfecta Type II (poor mineralization—often the proximal aspect of the brain is well seen through the “transparent” skull--, variable micromelia, sometimes visible bone angulations from fractures, bell shaped chest)

·         Diastrophic dysplasias in which the micromelia is associated with joint contractures and in particular abnormal finger and toes positions).

Prognosis: Children with Achondroplasia have normal intellectual achievements. The major problems are orthopedic problems (narrow spinal canal and foramen magnum). There is a vibrant support group (The Little People of America[4]) that is very active in resolving the problems of affected individual.

Management: Although termination of pregnancy can be offered before viability, a majority of these children adapt well in society and lead productive lives.

 

Figure 1: Short limb (in this image the arm). Note the polyhydramnios (esophageal compression from short ribs).

Figure 2: Frontal bossing

Figure 3: Lack of widening of the spinal canal

Reference:


[1] Velinov, M.; Slaugenhaupt, S. A.; Stoilov, I.; Scott, C. I., Jr.; Gusella, J. F.; Tsipouras, P. : The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nature Genet. 6: 318-321, 1994.

[2] Le Merrer, M.; Rousseau, F.; Legeai-Mallet, L.; Landais, J.-C.; Pelet, A.; Bonaventure, J.; Sanak, M.; Weissenbach, J.; Stoll, C.; Munnich, A.; Maroteaux, P. : A gene for achondroplasia--hypochondroplasia maps to chromosome 4p. Nature Genet. 6: 314-317, 1994

[3] Bellus, G. A.; Hefferon, T. W.; Ortiz de Luna, R. I.; Hecht, J. T.; Horton, W. A.; Machado, M.; Kaitila, I.; McIntosh, I.; Francomano, C. A. : Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am. J. Hum. Genet. 56: 368-373, 1995

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