Clinical Variability in Achondroplasia
It is well known that dominant disorders, in general, are characterized by extreme variability in phenotypic expression, but in achondroplasia the range of clinical variability had been considered to be narrow. Our studies show that achondroplasia does, in fact, have the marked clinical variability that exists in most autosomal dominant disorders. A quantitative estimate of the variability in achondroplasia can be obtained by calculating the range of adult height and head circumference measurements in this disorder. Examination of the standard growth charts which have been prepared for achondroplasia with those of individuals of normal stature, demonstrates that 1 SD for adult height in achondroplasia is 6.75 cm., as opposed to 6.65 cm. for normals (1). If one considers that the mean height of the achondroplasts is significantly less than that of the normal and then calculates the percentage of mean height that the standard deviation represents (coefficient of variation), the variability among achondroplasts appears even greater than that among controls (ISD/x × 100% for height = 3.8% for normals and 5.2% for achondroplasts). The increased variability among achondroplasia is even more striking when one examines head circumference, as 1 SD for the adult achondroplastic head circumference is 2.25 cm., as compared to 1.33 cm. for the normals, a difference which is statistically significant (p< 0.01). Thus on a quantitative basis, the variability among achondroplasts for adult height and head circumference is similar to or even greater than that among the normal population.
KeywordsHead Circumference Marfan Syndrome Adult Height Clinical Variability Small Foramen
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