Genetic studies of congenital contractures of limbs

ABSTRACT

Congenital contractures of limbs comprise a category of limb malformations that poses a difficult diagnostic and therapeutic problem. They can occur as an isolated defect or as part of syndromes. This study included 46 patients with congenital contractures of limbs. Cases were referred to the Limb and Skeletal Anomaly Clinic at the National Research Centre. Detailed family history, pedigree construction, physical and orodental examination, anthropometric measurements and radiological studies were carried out for all cases. Cytogenetic analysis using G-banding and high resolution techniques were carried out for 36 cases. Biochemical and neurophysiologic studies were conducted for selected cases. According to clinical phenol-type, cases were classified into 4 main categories, which were further subdivided into 16 entities. Category [I] included congenital contractures that affected primarily the musculoskeletal system, 18 cases were in this category comprising 8 entities. Category [II] Twenty cases had musculoskeletal involvement in addition to other system malformations or anomalies comprising 5 entities, of which 11 cases had multiple pterygium syndrome. Category [III] Six patients in this study had musculoskeletal involvement plus lethality, CNS anomalies or mental retardation. Four were diagnosed as Pena-Shokeir syndrome, one with Aase-Smith syndrome and another case showed dup [1] [p36.1-36.2]. Category [IV] Contracture deformities of limbs due to environmental factors, which were present in 2 cases only. Detailed genetic and clinical analysis of different cases with congenital contractures of limbs are presented in this study. Our work proved that contracture deformities of limbs due to genetic causes were the most common [44 cases], while those related to environmental causes were only present in 2 cases. This emphasizes the importance of careful clinical examination and categorization o patients with congenital contracture! of limbs and the necessity of proper genetic counseling of affected families. The study of the molecular causes of these disorders is important for the understanding of the pathogenesis hoping for their prevention, early intervention and gene therapy