Absence of Neurodevelopmental Impairment in an Individual With KCNN3-Related Zimmermann Laband Syndrome

Am J Med Genet A. 2025 May 13:e64113. doi: 10.1002/ajmg.a.64113. Online ahead of print.

ABSTRACT

Zimmermann-Laband syndrome (ZLS) is a rare group of potassium channelopathies presenting with characteristic facial findings, gingival hyperplasia, hypertrichosis, hypoplasia of phalanges and nails, neurodevelopmental disorders, and intellectual disability. KCNN3 related ZLS3 has been recently recognized. We detected a de novo heterozygous c.1606G>A variant in the KCNN3 gene using clinical exome sequencing. Our patient presented facial dysmorphism, ptosis and strabismus, pectus excavatum, hypertrichosis of the trunk and limbs, tapering fingers, hypoplastic nails, and gingival hyperplasia but no neurodevelopmental disorder or behavioral problems. To the best of our knowledge, our case is the ninth case of ZLS3 syndrome in the literature. We report a further case of ZLS3 without intellectual disability who, in addition, had a normal development as an infant. Previous cases of monozygotic twins were reported carrying the same variant in the KCNN3 gene. Twin sisters carrying the same variant in our study were reported to have developmental delay, but their intellectual level is normal in adulthood. We suggest KCNN3 related ZLS3 may not be associated with any neurodevelopmental disorder; that is an important issue for genetic counseling.

PMID:40358131 | DOI:10.1002/ajmg.a.64113