Genetic Studies of Limb Reduction Defects

Limb reduction defects are an important group of congenital limb malformations that requires thorough assessment. They can be isolated or associated with other malformations as a part of syndrome. Causes of limb deficiencies include single gene disorders, chromosomal abnormalities or teratogens. However, the etiology remains unknown in many cases. The present study aimed at the proper diagnosis and classification of cases with limb defects referred to the Limb Malformations Clinic, NRC in order to provide accurate and efficient genetic counseling. The study included 22 cases (14 males, 8 females) with limb reduction defects, their ages at presentation ranged between 20 days and 16 years. Detailed history including teratogen exposure and affected family members, three generation pedigree analysis, complete examination of different body systems with specific studies of different parts of the limbs documented by radiological examination, photography and basic anthropometric measurements were conducted for all cases. Dermatoglyphic analysis, cytogenetic studies and other investigations were done whenever indicated. Cases were classified according to Temtamy and McKusick (1) based on both anatomical and genetic considerations into 8 groups; isolated terminal transverse defects (n=5, cases 1-5= 22.7%), terminal transverse defect as a part of syndrome (n=1, case 6= 4.54%), isolated radial defect (n=1, case 7= 4.54%), radial defect as a part of syndrome (n= 7, cases 8-14= 31.8%), isolated ulnar defect (n= 2, cases 15, 16= 9.09%), ulnar defect as a part of syndrome (n= 3, cases 17- 19= 13.6%), pre and postaxial defect (n= 1, case 20= 4.54%) and axial defect as a part of syndrome (n=2, cases 21, 22= 9.09%). The results of this study have shown that limb absence or reduction defects are not an uncommon malformation among Egyptian children. Delineation of the exact cause, correct classification and proper diagnosis are needed to face this disabling chronic problem. Molecular studies are recommended for proper diagnosis, genetic counseling and understanding of the pathogenesis.