The Phenotypic Association of Transverse and Central Ray Limb Deficiencies. A.M. Elliott, J.A. Evans Dept Biochem & Medical Gen, Univ Manitoba, Winnipeg, MB, Canada.
Central ray deficiency (Split Hand Foot Malformation, SHFM) can occur as an isolated anomaly or in association with other malformations. Classifications of SHFM include typical (central V-shaped cleft, often multimelic with positive family history) or atypical (central deficiency, sporadic, one affected limb). Typical SHFM is considered more genetic in nature and atypical more vascular. The most severe expression of typical SHFM is considered to be fifth finger monodactyly. However, Maisels proposed the Centripetal Suppression Theory that explains split hand as a progressive insult to the developing hand plate ranging from a simple cleft with no tissue deficiency to the most severe formaphalangiaa terminal transverse defect (TTD) (Hand, 1970). Geneticists generally associate TTD with vascular insult. We performed a detailed clinical epidemiologic study to investigate the association of central ray deficiency and TTD. Isolated and syndromic patients were evaluated from the literature and the local (Manitoba) population. Inclusion criteria consisted of central ray deficiency and TTD in the same patient. This phenotypic combination was seen in both syndromic and isolated SHFM patients. Syndromic cases included those with long bone deficiency (e.g. tibial aplasia/ectrodactyly, femur-fibula-ulna complex). It was also associated with ulnar deficiency, hypoglossia-hypodactyly, chromosome anomalies and mutations in TP63. The underlying genetic defect, if any, has not been elucidated for many of these disorders. The finding of this phenotypic combination in the same patient suggests TTD are not exclusively vascular in nature and likely represent the most severe expression of SHFM, thus supporting Maisels' theory.