van den Ende–Gupta syndrome of blepharophimosis, arachnodactyly, and congenital contractures: Clinical delineation and recurrence in brothers

We describe two Hispanic brothers born to unrelated parents with van den Ende-Gupta syndrome (VDEGS), a distinctive combination of characteristic dysmorphic features, skeletal abnormalities, and cerebellar hyperplasia. This syndrome was previously delineated by van den Ende et al. [1992: Am J Med Genet 42:467-469] and Gupta et al. [1995: J Med Genet 32:809-812], with additional reports by Phadke et al. [1998: Am J Med Genet 77:16-18] and Bistritzer et al. [1993: Clin Genet 44:15-19]. This is the fifth report of VDEGS, which is characterized by blepharophimosis, narrow nose with hypoplastic alae nasi, hypoplastic maxilla, everted lower lip, slender and elongated hands and feet, arachnodactyly, self-limiting joint contractures, and distinctive skeletal findings. This report of affected siblings, and a previous report of double second cousins born to consanguineous parents [Bistritzer et al. [1993: Clin Genet 44:15-19]], suggests autosomal recessive inheritance. This brings to eight, the total number of reported cases, derived from six families, three of which are consanguineous. It is important to distinguish VDEGS from Marden-Walker syndrome (MWS) since both syndromes include blepharophimosis, arachnodactyly, and congenital contractures. Both syndromes are inherited in an autosomal recessive fashion, but VDEGS lacks severe mental retardation, serious brain malformations, microcephaly, failure to thrive, and severe joint limitation, which are consistently present in MWS. Of particular importance, MWS may be associated with cerebellar malformations such as Dandy-Walker malformation, while the brothers reported herein with VDEGS both demonstrated distinctive cerebellar enlargement, a new finding for this disorder. While, congenital contractures with arachnodactyly are features commonly seen in several other delineated syndromes, such as congenital contractural arachnodactyly (CCA) syndrome, characteristic facial features (blepharophimosis, narrow nose with ocular hypertelorism, prominent ears, and everted lower lip), distinguish VDEGS from other syndromes associated with CCA, including CCA.