HETEROZYGOUS MANIFESTATIONS IN THE HERITABLE DISORDERS OF THE SKELETON

Many heritable disorders of the skeleton are transmitted as autosomal recessive (AR) traits. During the past two decades, family studies hav e been undertaken in conditions of this type in order to detect any st ructural manifestations in obligate and potential heterozygotes. The p ositive findings that emerge from this long-term investigation are rep orted. In numerous other AR skeletal disorders family investigations f ailed to reveal any significant abnormalities in relatives of affected persons. A review of the literature elicited additional examples of h eterozygote manifestation. The skeletal abnormalities in the heterozyg otes are usually inconsistent and often innocuous, but they have a num ber of important implications: (a) identification of heterozygotes for family screening or for genetic counseling; (b) identification of het erozygotes for conventional and molecular linkage studies; (c) problem s with pedigree analysis; variable expression of an autosomal dominant trait versus heterozygous manifestations in an AR disorder; (d) probl ems with diagnosis, e.g., does a congenital Madelung anomaly always re present the heterozygous form of Langer mesomelic dysplasia? What prop ortion of persons with isolated brachydactyly are heterozygotes for Gr ebe chondrodysplasia? It is likely that close scrutiny of first-degree relatives of persons with other AR skeletal disorders will reveal exa mples of heterozygous manifestations.