spondylocostal dysostosis . kindred with autosomal recessive expression in a large inbred Evidence for variable gene

Seven members of a large inbred kindred with autosomal recessive spondylocostal dysostosis were examined clinically, radiographicaily, and sonographically. The subjects were three adults, one adolescent, and three children under 3 years of age. One child was the offspring of a first cousin marriage which showed quasi-dominant inheritance. Six subjects had short stature owing to widespread vertebral dyssegmentation with variable reduction in rib number and rib fusion. One subject was of normal stature, had limited vertebral dyssegmentation, an extra rib, and no rib fusion. Five subjects showed the plagiocephaly-torticollis sequence. Four of the five male subjects had inguinal herniation on one or both sides. All subjects had normal renal ultrasonography. The youngest subject died of cardiopulmonary complications and is thought to represent one extreme in the expressivity of the gene in this kindred. Spondylocostal dysostosis is a heterogeneous disorder of vertebral dyssegmentation in which three distinct entities are clearly described. Jarcho and Levin' were the first to describe a severe autosomal recessive form of a syndrome which now bears their names and is also referred to as spondylocostal dysostosis type I. In this condition, abnormal vertebral segmentation is often associated with a decreased number of ribs which have a 'crowded' origin from the thoracic Paediatric Department, The Nazareth Hospital, PO Box 11, 16100 Nazareth, Israel. P D Turnpenny, R J Thwaites Radiology Department , The Nazareth Hospital, PO Box 11, 16100 Nazareth, Israel. F N Boulos Correspondence to Dr Turmpenny, Department of Medical Genetics, Aberdeen University Medical School, Foresterhill, Aberdeen AB9 2ZB. Received for publication 29 May 1990. Accepted for publication 22 June 1990. vertebral bodies and 'fan out' to give a characteristic 'crab-like' appearance of the thorax on x ray. Death in infancy owing to respiratory insufficiency is the rule. Further reports of this condition have highlighted a Puerto Rican ancestry in many cases.25 The condition is amenable to prenatal diagnosis by ultrasonography.-7 A benign form of spondylocostal dysostosis showing autosomal dominant inheritance has been described.8-10 The main complications are relative immobility of the spine and pain and weakness associated with an upright posture. Benign autosomal recessive spondylocostal dysostosis is the most frequently described entity within the group.7 11-18 Within this entity, however, there are different phenotypes with, for instance, obvious differences in the shoulder span between cases described by Beighton and Horan,'7 and those described by Castroviejo et al. 12 In addition, a variety of associated malformations have been described,'92' often relating to the structures which arise from the paraxial mesoderm in embryological life. Such cases begin to resemble malformations following the VATER or VACTERL pattern. There is an additional category of cases of spondylocostal dysostosis associated with miscellaneous malformations.22-24 An attempt has been made to delineate the groups by phenotype cluster analysis.21 The subjects of this study are an Arab family who were identified after the birth of two children in the pedigree, subjects V1.1 and V1.3 in fig 1. It was decided to examine them clinically, radiographically, and the renal system non-invasively by ultrasound. Seven subjects were identified and this is thought to be the largest number so far available for study within a single kindred. Materials and methods The pedigree (fig 1) was constructed from our own knowledge of the family and from data available from the area cytogenetics service. Affected subjects were identified by direct questioning of the family. A clinical examination was conducted and the following data obtained: height, sitting height, span, and head and chest circumference. 27 group.bmj.com on June 21, 2017 Published by http://jmg.bmj.com/ Downloaded from