Extending the phenotypic spectrum of Bohring-Opitz syndrome: Mild case confirmed by functional studies

摘要

Bohring-Opitz syndrome (BOS) has been described as a clinically recognizable genetic syndrome since 1999. Clinical diagnostic criteria were established in 2011 and include microcephaly, trigonocephaly, distinctive craniofacial dysmorphic features, facial nevus flammeus, failure to thrive, and severe developmental delays. The same year, different de novo heterozygous nonsense mutations in the ASXL1 were found in affected individuals. Since then, several cases have been reported confirming the association between this chromatin remodeling gene and BOS. Most affected individuals die in early childhood because of unexplained bradycardia, obstructive apnea, or pulmonary infections. Those that survive usually cannot walk independently and are nonverbal. Some have had success using walkers and braces in late childhood. While few are able to speak, many have been able to express basic needs using communication devices as well as gestures with associated basic vocalizations. In this article, we present a mild case of BOS with a de novo pathogenic mutation c.1720-2A>G (p.I574VfsX22) in ASXL1 detected on whole-exome sequencing and confirmed by functional analysis of the messenger RNA splicing pattern on the patient's fibroblasts. She has typical dysmorphic features and is able to run and walk independently as well as to communicate with basic sign language.