RESUMEN
Christianson syndrome (OMIM 300243), caused by mutations in the X-linked SLC9A6 gene, is characterized by severe global developmental delay and intellectual disability, developmental regression, epilepsy, microcephaly and impaired ocular movements. It shares many common features with Angelman syndrome. Carrier females have been described as having learning difficulties with mild to moderate intellectual disability, behavioural issues and psychiatric illnesses. There is little literature on the carrier female phenotype of Christianson syndrome. We describe a large extended family with three affected males, four carrier females, one presumed carrier female and one obligate carrier female with a c.190G>T, p.E64X mutation known to cause a premature stop codon in SLC9A6. We characterize and expand the clinical phenotype of female SLC9A6 mutation carriers by comparing our described family with female carriers previously discussed in the literature. In particular, we highlight the neurodevelopmental and psychiatric phenotypes observed in our family and previous reports.
Asunto(s)
Síndrome de Angelman/genética , Ataxia/genética , Epilepsia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Discapacidad Intelectual/genética , Microcefalia/genética , Trastornos de la Motilidad Ocular/genética , Intercambiadores de Sodio-Hidrógeno/genética , Síndrome de Angelman/fisiopatología , Ataxia/fisiopatología , Codón sin Sentido/genética , Epilepsia/fisiopatología , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Heterocigoto , Humanos , Discapacidad Intelectual/fisiopatología , Discapacidades para el Aprendizaje/genética , Discapacidades para el Aprendizaje/fisiopatología , Masculino , Microcefalia/fisiopatología , Mutación , Trastornos de la Motilidad Ocular/fisiopatología , LinajeRESUMEN
BACKGROUND: Interstitial deletions at chromosome 8q22.2-q22.3 have been rarely reported in the literature. To date, six patients have been described in the literature with deletions varying in size from 1.36 Mb to 6.44 Mb. These patients range in age from early childhood to early adulthood. The interstitial deletion phenotype has been described to involve moderate to severe intellectual disability, seizures and a distinct facial phenotype. We report on a 40-year-old male with a 3.351 Mb deletion at chromosome 8q22.2-q22.3 who presents with moderate intellectual disability, autism spectrum disorder, childhood seizure disorder, congenital heart defect and hearing loss. He is the oldest known patient to date. METHODS: Array comparative genomic hybridization (aCGH) was performed on DNA extracted from peripheral blood. CONCLUSION: This is the first report of an individual with chromosome 8q22.2-q22.3 interstitial deletion associated with congenital heart disease and hearing loss. Haploinsufficiency of the GRHL2 gene contained within the microdeletion is proposed as a candidate genetic mechanism for this patient's hearing loss.