ZMYM2 heterozygous pathogenic variants cause an ultra-rare disease characterized by a broad clinical phenotype. This condition has been named neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (NECRC, MIM#619522). Associated anomalies include congenital abnormalities of the kidney and urinary tract (CAKUT), non-specific facial, cardiac, and skeletal abnormalities, along with a variety of neurodevelopmental disorders. Other abnormalities reported in some patients include infantile hypotonia, poor growth, microcephaly, hypospadias, and motor stereotypies. Recently, one patient with cerebral palsy embedded in a complex phenotype was reported to carry a pathogenic ZMYM2 variant.
This study presents the case of a 13-year-old girl carrying a de novo ZMYM2 heterozygous pathogenic variant. The patient displayed a Rett-like phenotype, associated with non-specific features such as precocious puberty, short stature, facial dysmorphisms, and spastic diplegia.
This case expands the known clinical phenotype associated with ZMYM2 pathogenic variants, suggesting for the first time a possible link to Rett-like syndromes.