Clinical characteristics: Gabriele-de Vries syndrome is characterized by mild-to-profound developmental delay / intellectual disability (DD/ID) in all affected individuals and a wide spectrum of functional and morphologic abnormalities. Intrauterine growth restriction or low birth weight and feeding difficulties are common. Congenital brain, eye, heart, kidney, genital, and/or skeletal system anomalies have also been reported. About half of affected individuals have neurologic manifestations, including hypotonia and gait abnormalities. Behavioral issues can include attention-deficit/hyperactivity disorder, anxiety, autism or autistic behavior, and schizoaffective disorder.
Diagnosis/testing: The diagnosis of Gabriele-de Vries syndrome is established in a proband by the identification of a heterozygous pathogenic variant involving YY1 or a heterozygous deletion of 14q32.2 involving only YY1.
Management: Treatment of manifestations: Developmental delay / intellectual disability, craniofacial anomalies (Pierre Robin sequence, cleft palate, craniosynostosis, abnormalities of the lacrimal duct), feeding difficulties, gastroesophageal reflux, constipation, seizures, behavioral manifestations, strabismus, refractive error, congenital heart defects, renal anomalies, cryptorchidism, and skeletal anomalies are treated per standard practice.
Surveillance: Of clinical manifestations as clinically indicated.
Genetic counseling: Gabriele-de Vries syndrome is inherited in an autosomal dominant manner. All probands reported to date with Gabriele-de Vries syndrome whose parents have undergone molecular genetic testing have the disorder as a result of a de novo YY1 pathogenic variant or deletion. Risk to future pregnancies is presumed to be low as the proband most likely has a de novo YY1 pathogenic variant or deletion; however, given the theoretic possibility of parental germline mosaicism, recurrence risk to sibs is estimated at 1%, and thus prenatal and preimplantation genetic testing may be considered.
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