van den Ende–Gupta syndrome: Evidence for genetic heterogeneity

Abstract

van den Ende-Gupta syndrome is characterized by craniofacial and skeletal manifestations, mainly malar and/or maxillary hypoplasia, blepharophimosis, distinctive nose, lower lip eversion, arachnodactyly, camptodactyly, and long slender bones of hands and feet. Growth and development are normal. To date only 11 patients, from 8 families, have been described. Autosomal recessive inheritance has been accepted in this condition, supported by the presence of consanguinity in three families and the recurrence of the disorder within the offspring of unaffected couples. In this article we report on a kindred with three affected individuals, two brothers and their half-sister, in which the van den Ende-Gupta syndrome is probably transmitted as an autosomal dominant trait in connection with gonadal mosaicism.

Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome

“…Further patients with this constellation of anomalies have been reported, reinforcing the hypothesis of an autosomal recessive mode of inheritance [Bistritzer et al, 1993;Schweitzer et al, 2003;Carr et al, 2007;Ali et al, 2010]. Only one report by Leal and Silva [2009] suggested genetic heterogeneity and an autosomal dominant trait based on the observation of 3 affected individuals, 2 brothers and their half-sister, assuming gonadal mosaicism.…”

“…Recently, because 3 affected individuals, 2 brothers and their half-sister, were reported, Leal and Silva [2009] hypothesized an autosomal dominant transmission and gonadal mosaicism, suggesting genetic heterogeneity. However, we consider it more likely, that all 3 half-siblings are by change carriers of recessive mutations, a hypothesis that could now be proven.…”

Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

“…It was first delineated by van den Ende et al and Gupta et al 1,2 To date, only 14 patients from nine families have been described. [1][2][3][4][5][6][7] Inheritance is likely autosomal recessive, which is supported by consanguinity of affected matings, the recurrence of the disorder among the offspring of unaffected couples, and equal sex involvement. 2,7 It is characterized by craniofacial abnormalities that include blepharophimosis, a flat and wide nasal bridge, malar and/or maxillary hypoplasia, prominent ears, a narrow and beaked nose, an everted lower lip, palatal abnormalities, and down-slanting eyes.…”

“…Skeletal abnormalities include camptodactyly, arachnodactyly, long thumbs, and hallux valgus. Patients can have flexion contractures 5 and skeletal findings, such as slender ribs, hooked clavicles, and bowed long bones. [1][2][3][4]6,8 Respiratory problems due to laryngeal abnormalities have also been described in some patients.…”

“…7 The case for clinical heterogeneity in VDEGS has been made. 5 One mother had affected children with two different nonrelated partners. The authors postulated that in this pedigree, VDEGS was inherited in a dominant manner, possibly as a result of gonadal mosaicism.…”