关键词: Menke-Hennekam 综合征, Rubinstein-Taybi综合征, 智力障碍, 发育迟缓, CREBBP基因, 基因变异

Abstract:

ObjectiveTo explore the clinical phenotype and identify genetic variations in Chinese patients with Menke-Hennekam syndrome (MKHK). Methods The clinical and genetic data of seven children with MKHK were retrospectively analyzed. Results All of the seven children are presented with psychomotor developmental delay, variable degree of intellectual disability, short stature, and facial dysmorphism (including short and upslanted palpebral fissures, telecanthi, depressed nasal bridge, short nose, long philtrum, protruding or low-set ears and micrognathia), accompanied by other manifestations (2/7 feeding problems, 4/7 visual impairment, 3/7 hearing impairment, 3/7 cerebral anomaly, 2/7 distal limb malformation). The genetic findings of patientsinvolve six different variants: five missense and one in-frame deletion), all of which arose de novo. c.5218C>T and c.5225T>A (NM_004380.3) variants have not been reported previously in literature. Conclusion MKHK is a rare autosomal dominant genetic disease, most of which are caused by heterozygous missense variation in the end of exon 30 and the beginning of exon 31 of CREBBP. This study revealed six de novo variants of CREBBP, further expanding the genetic spectrum of MKHK.

Key words: Menke-Hennekam syndrome, Rubinstein-Taybi syndrome, intellectual disability, developmental delay, CREBBP gene, genetic variation