The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities.
In this report, we describe six unrelated patients with newly diagnosed heterozygous de novo loss-of-function variants in ASXL3 and concordant clinical features: severe muscular hypotonia with feeding difficulties in infancy, significant motor delay, profound speech impairment, intellectual disability and a characteristic craniofacial phenotype (long face, arched eyebrows with mild synophrys, downslanting palpebral fissures, prominent columella, small alae nasi, high, narrow palate and relatively little facial expression).