Cantú syndrome (CS) is a rare developmental disorder characterized by a coarse facial appearance, macrocephaly, hypertrichosis, skeletal and cardiovascular anomalies and caused by heterozygous gain-of-function variants in ABCC9 and KCNJ8, encoding subunits of heterooctameric ATP-sensitive potassium (K_ATP) channels. CS shows considerable clinical overlap with Zimmermann-Laband syndrome (ZLS), a rare condition with coarse facial features, hypertrichosis, gingival overgrowth, intellectual disability of variable degree, and hypoplasia or aplasia of terminal phalanges and/or nails. ZLS is caused by heterozygous gain-of-function variants in KCNH1 or KCNN3, and gain-of-function KCNK4 variants underlie the clinically similar FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth) syndrome; KCNH1, KCNN3 and KCNK4 encode potassium channels. Within our research project on ZLS, we performed targeted Sanger sequencing of ABCC9 in 15 individuals tested negative for a mutation in the ZLS-associated genes and found two individuals harboring a heterozygous pathogenic ABCC9 missense variant. Through a collaborative effort, we identified a total of nine individuals carrying a monoallelic ABCC9 variant: five sporadic patients and four members of two unrelated families. Among the six detected ABCC9 missense variants, four [p.(Pro252Leu), p.(Thr259Lys), p.(Ala1064Pro), and p.(Arg1197His)] were novel. Systematic assessment of the clinical features in the nine cases with an ABCC9 variant highlights the significant clinical overlap between ZLS and CS that includes early developmental delay, hypertrichosis, gingival overgrowth, joint laxity, and hypoplasia of terminal phalanges and nails. Gain of K⁺ channel activity possibly accounts for significant clinical similarities of CS, ZLS and FHEIG syndrome and defines a new subgroup of potassium channelopathies.

Cantú综合征（CS）是一种罕见的发育障碍，其特征是面部表情粗糙，大头畸形，肥大症，骨骼和心血管异常，并由ABCC9和KCNJ8的杂合功能获得变异体引起，该变异体编码杂八聚ATP敏感性钾（K _ATP）渠道。CS显示出与Zimmermann-Laband综合征（ZLS）的大量临床重叠，Zimmermann-Laband综合征（ZLS）是一种罕见的疾病，面部特征粗大，肥大，牙龈过度生长，智力不同程度的残疾以及指骨和/或指甲发育不全或发育不良。ZLS是由KCNH1或KCNN3中的杂合功能获得变体和KCNK4引起的背后临床类似FHEIG变体（˚F acial异形，ħ ypertrichosis，ê pilepsy，我ntellectual残疾/发育迟缓，和克ingival过度生长）综合征; KCNH1，KCNN3和KCNK4编码钾通道。在我们关于ZLS的研究项目中，我们对15位测试为ZLS相关基因突变阴性的个体进行了针对ABCC9的靶向Sanger测序，发现两名个体带有杂合致病性ABCC9错义变体。通过合作，我们确定了总共有9个人携带等位基因ABCC9变体：五位散发患者和两个不相关家庭的四位成员。在六个检测到的ABCC9错义变体中，四个[p。（Pro252Leu），p。（Thr259Lys），p。（Ala1064Pro）和p。（Arg1197His）]是新颖的。对9例ABCC9变体的临床特征进行系统评估，突显了ZLS和CS之间的重大临床重叠，包括早期发育延迟，过度肥大，牙龈过度生长，关节松弛以及末端指骨和指甲发育不全。K ⁺通道活性的获得可能解释了CS，ZLS和FHEIG综合征的重大临床相似性，并定义了钾通道病的新亚组。