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P63 mutations are not a major cause of non-syndromic split hand/foot malformation
  1. X J de Mollerat1,
  2. D B Everman1,2,
  3. C T Morgan1,
  4. K B Clarkson1,
  5. R C Rogers1,
  6. R S Colby1,
  7. A S Aylsworth3,
  8. J M Graham, Jr4,
  9. R E Stevenson1,2,
  10. C E Schwartz1,2
  1. 1Center for Molecular Studies, J C Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina, USA
  2. 2Department of Genetics and Biochemistry, Clemson University, South Carolina, USA
  3. 3Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA
  4. 4Medical Genetics Birth Defects Center, Department of Pediatrics, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA
  1. Correspondence to:
 Dr C Schwartz, Center for Molecular Studies, J C Self Research Institute, One Gregor Mendel Circle, Greenwood, SC 29646, USA; 
 schwartz{at}ggc.org

https://doi.org/10.1136/jmg.40.1.55

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    Ectrodactyly or split hand/foot malformation (SHFM) is a human limb malformation characterised by underdevelopment or absence of the central digital rays and variable fusion of the remaining digits (MIM 183600). This condition occurs in 1 in 8500–25 000 newborns1–4 and is usually inherited in an autosomal dominant manner, although a family with an X linked form has also been reported.5 At least five loci are responsible for this condition in humans: SHFM1 on 7q21.3-q22.1,6,7 SHFM2 on Xq26,5,8 SHFM3 on 10q24,9,10 SHFM4 on 3q27,11 and SHFM5 on 2q31.12,13

    SHFM is clinically heterogeneous, presenting in either non-syndromic or syndromic forms. The non-syndromic form of SHFM can be isolated (type I) or associated with long bone deficiency (type II).14 The latter disorder has several names, including cleft hand with absent tibia and SHFM with long bone deficiency (SHFLD (MIM 119100)). Patients with SHFLD have SHFM in association with underdevelopment or absence of one or more long bones, most commonly the tibia.14–18 As with other forms of SHFM, the pattern of limb deficiency in SHFLD may be widely variable, even among the limbs of an affected subject. This condition preferentially affects males (M:F 1.6:1), right sided limbs, and lower limbs.16 Other skeletal findings in SHFLD include hypoplastic hallux, club foot, polydactyly, and bifurcation of the distal femur.15 Although ectodermal dysplasia19,20 and other findings have been seen in some patients with SHFLD, no consistent pattern of non-skeletal anomalies has been observed.

    The prototypical syndromic form of SHFM is the EEC syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate) (MIM 129900).21 The EEC phenotype includes SHFM, orofacial clefts, and abnormalities of the skin, teeth, hair, nails, lacrimal ducts, and mammary glands.21 Interestingly, penetrance in SHFLD (66%) …

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