Abstract
Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel (AA/RRS) phocomelia syndrome are rare autosomal recessive inherited disorders characterized by aplastic/hypoplastic nails with ectopic dorsal palms, absence of humeri, hypoplastic ulnae, and bowed short radii with the elbow joints present, shown to result from missense mutations in WNT7A (p.Ala109Thr and p.Arg292Cys). Here, we describe three affected individuals belonging to two related Saudi Arabian families. All three have a similar phenotype characterized by pelvic dysplasia and truncated lower limbs compatible with the clinical diagnosis of AA/RRS. The upper limbs were more variable: one patient individual had complete amelia, whereas the others had variable limb malformations and all had absence of nails and the ventralization of the palms/digits. All affected individuals were homozygous for a mutation in exon 4 of WNT7A(c.610G > A) resulted in substitution of a highly conserved glycine to serine (p. Gly204Ser) within the Wnt signaturemotif [C-K-C-H-G-V-S-G-S-C]. This report describes a third cases/family in the literature with variable phenotype of AA/RRS and Fuhrmann syndrome. Identification of this mutation further underlines the crucial involvement of WNT7A in the limb development. This novel missense homozygous mutation (p. Gly204Ser) in the WNT7 Agene is a unique mutation in the degree of loss of function in the upper limb development which ranges from mild to complete absence of both upper limbs (amelia). Moreover, all three affected individuals had genitourinary anomalies, linking WNT7A function to genitourinary development. (C) 2011 Wiley-Liss, Inc.