A de novo ZMYM2 gene variant associated to a Rett-like phenotype: Case report of a new phenotype and review of the literature.

BACKGROUND

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.

CASE PRESENTATION: 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.

CONCLUSIONS

This case expands the known clinical phenotype associated with ZMYM2 pathogenic variants, suggesting for the first time a possible link to Rett-like syndromes.