Zimmermann-Laband Syndrome (ZLS; MIM 135500) is a rare genetic disorder with the main clinical manifestations of gingival fibromatosis and finger/toe nail hypoplasia. KCNH1 (potassium channel, voltage-gated, subfamily H, member-1), KCNN3 (potassium channel, voltage-gated, subfamily H, member-3) and ATP6V1B2 (ATPase H+ transporting V1 subunit B2) genes are considered causative genes for ZLS. However, there are limited reports about the diverse clinical presentation and genetic heterogeneity. Reporting more information on phenotype-genotype correlation and the treatment of ZLS is necessary. This case reported a 2-year-old patient with gingival enlargement that failure of eruption of the deciduous teeth and severe hypoplasia of nails. Based on a systemic examination and a review of the relevant literature, we made an initial clinical diagnosis of ZLS. A novel pathogenic variant in the KCNH1 gene was identified using whole-exome sequencing to substantiate our preliminary diagnosis. The histopathological results were consistent with gingival fibromatosis. Gingivectomy and gingivoplasty were performed under general anesthesia. After surgery, the gingival appearance improved significantly, and the masticatory function of the teeth was restored. After 2-year follow-up, the gingival showed slightly hyperplasia. Systemic examination and gene sequencing firstly contribute to provide information for an early diagnosis for ZLS, then timely removal of the hyperplastic gingival facilitates the establishment of a normal occlusal relationship and improves oral aesthetics.

Genotype-phenotypic correlation of KCNH1 variant remains elusive. This study aimed to expand the phenotypic spectrum of KCNH1 and explore the correlations between epilepsy and molecular sub-regional locations.
We performed whole-exome sequencing in a cohort of 98 patients with familiar febrile seizure (FS) or epilepsy with unexplained etiologies. The damaging effects of variants were predicted by protein modeling and multiple in silico tools. All reported patients with KCNH1 pathogenic variants with detailed neurological phenotypes were analyzed to evaluate the genotype-phenotype correlation.
Two novel KCNH1 variants were identified in three cases, including two patients with FS with inherited variant (p.Ile113Thr) and one boy with epilepsy with de novo variant (p.Arg357Trp). Variant Ile113Thr was located within the eag domain, and variant p.Arg357Trp was located in transmembrane domain 4 of KCNH1, respectively. Two patients experienced refractory status epilepticus (SE), of which one patient died of acute encephalopathy induced by SE. Further analysis of 30 variants in 51 patients demonstrated that de novo variants were associated with epileptic encephalopathy, while mosaic/somatic or germline variants cause isolated epilepsy/FS. All hotspot variants associated with epileptic encephalopathy clustered in transmembrane domain (S4 and S6), while those with isolated epilepsy/seizures or TBS/ZLS without epilepsy were scattered in the KCNH1.
We found two novel missense variants of KCNH1 in three individuals with isolated FS/epilepsy. Variants in the KCNH1 cause a spectrum of epileptic disorders ranging from a benign form of genetic isolated epilepsy/FS to intractable form of epileptic encephalopathy. The genotypes and variant locations help explaining the phenotypic variation of patients with KCNH1 variant.