Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred

• Published in: American journal of medical genetics 1998-08, Vol.78 (5), p.468-473
• Main Authors: Ahmad, Mahmud, Ul Haque, Muhammad Faiyaz, Ahmad, Wasim, Abbas, Hasan, Haque, Sayedul, Krakow, Deborah, Rimoin, David L., Lachman, Ralph S., Cohn, Daniel H.
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Alleles; Biological and medical sciences; cartilage; chondrodysplasia; Consanguinity; Diseases of the osteoarticular system; dwarfism; Dwarfism - genetics; Female; Gait; Genes, Recessive; Hand Deformities, Congenital - diagnostic imaging; Hand Deformities, Congenital - genetics; Homozygote; Humans; Leg - abnormalities; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Osteoarthritis; Osteochondrodysplasias - genetics; Pakistan; Pedigree; Radiography; Scoliosis - diagnostic imaging; Scoliosis - genetics; spondyloepimetaphyseal dysplasia; Tropical medicine
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/(SICI)1096-8628(19980806)78:5<468::AID-AJMG13>3.0.CO;2-D

We describe a large inbred kindred from a remote area of Pakistan, comprising eight generations, with a distinct form of spondyloepimetaphyseal dysplasia (SEMD). We evaluated 16 affected individuals: 11 males and 5 females. Analysis of the pedigree strongly suggests autosomal recessive inheritance, and consanguineous loops could account for all the affected individuals being homozygous for the abnormal allele. The clinical findings included short stature evident at birth, short bowed lower limbs, mild brachydactyly, kyphoscoliosis, an abnormal gait, enlarged knee joints, precocious osteoarthropathy, and normal intelligence. Radiographs demonstrated delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse, early osteoarthritic changes, primarily in the spine and hands, and mild brachydactyly. Mild metaphyseal abnormalities were seen predominantly at hips and knees. This distinctive phenotype is distinct from other autosomal recessive forms of SEMD because of the mild degree of metaphyseal involvement, the type of brachydactyly, and the absence of loose joints or other clinical findings. Am. J. Med. Genet. 78:468–473, 1998. © 1998 Wiley‐Liss, Inc.