Masaru Higo

A family with an autosomal dominant mesomelic dysplasia resembling mesomelic dysplasia Savarirayan and Nievergelt types

Mesomelic dysplasia is a heterogeneous group of constitutional bone diseases, and its classification remains incomplete and controversial. In this group of disorders, the Nievergelt type has continuously attracted attention. The disorder is the most severe form of mesomelic dysplasia inherited as an autosomal dominant trait, and presents with a distinctive ‘‘triangular or rhomboid’’ deformity of the tibiae and radii. Recently, a new variant of mesomelic dysplasia resembling the Nievergelt type has been proposed, and currently cited as mesomelic dysplasia Savarirayan type in the International Nosology and Classification of Constitutional Disorders of Bone (2001) [Savarirayan et al., 2000; Hall, 2002; Monga et al., 2003]. Its mode of inheritance has not been yet determined. The Savarirayan type shows a triangular or oval deformity of the tibiae mimicking that of the Nievergelt type.However, the absence or hypoplasia of the fibulae and mild shortening of the forearm in the Savarirayan type contrast with the relative elongation of the fibulae and severe hypoplasia of the radii and ulnae in the Nievergelt type. The new revision of the International Nosology and Classification of Genetic Skeletal Disorders notes that Savarirayan type may be related to the Nievergelt type [Superti-Furga et al., 2007]. We report here on an affected father and son with a severe form of mesomelic dysplasia, which shares many features of both the Savarirayan and Nievergelt types. The proband was a Japanese boy born to a similarly affected father and a healthy mother. He was vaginally delivered at 38 weeks’ gestation after an unremarkable pregnancy. The birth weight was 2,136 g. He was referred to us at age 18 days because of his short lower legs. His weight was 2,580 g ( 1.6 SD), length 42.2 cm ( 3.9 SD), and OFC 33.4 cm ( 1.2 SD). The legs were very short with genu valgum. The ankles showed valgus deformity associated with pes cavus and metatarsus adductus. The arms were slightly short, while the hands were normal in length. Chromosome analysis showed a normal 46,XY karyotype. Laboratory examinations were normal. Motor development was slightly retarded: the subject stood with support at age 9 months, and walked unaided at 18 months. Mental development was normal. Valgus deformity of the ankle and knee exacerbated with age: it necessitated corrective surgeries at age 19 months and again at 3 years. At age 10 years, his height was 94 cm ( 7 SD) and weight 18 kg ( 2 SD). The 43-year-old father was 113 cm in height ( 9.5 SD). He had very short lower legs with genu valgum, ankle valgus, pes cavus, and metatarsus adductus. Movement of the elbow joints was restricted. The hands were unremarkable. Nevertheless, the physical disabilities did not interfere with his social activities. Radiological examinations of the proband at ages 6 months and 8 years showed a severe deformity of the shank and mild deformity of the forearm. The