PURPOSE Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized. METHODS We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum. RESULTS We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent. CONCLUSION Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.

中文翻译：

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进一步描述 KAT6B 疾病和等位基因系列致病变异的临床谱。

目的 Genitopatellar 综合征和 Say-Barber-Biesecker-Young-Simpson 综合征是由 KAT6B 基因的变异引起的，属于称为 KAT6B 疾病的广泛临床谱系的一部分，其可变表达性越来越得到认可。方法 我们在此展示了 32 名以前未报告过的具有 KAT6B 疾病分子诊断的个体的表型，报告了 24 种新的致病性 KAT6B 变异，并审查了所有已发表的患有这种疾病的个体的表型信息。我们还建议对 KAT6B 疾病谱中的临床亚型进行分类。结果 我们证明，除了长拇指和大脚趾外，大脑异常、视神经发育不全、神经行为障碍和远端肢体异常（如多指畸形）比最初报道的更常见。受影响的个体可能存在肠旋转不良及其严重后果。此外，我们还确定了 4 名具有 Pierre Robin 序列的儿童，4 名产前颈部透明质/囊性水瘤增加的个体，以及 2 名患有导致肾功能衰竭的严重肾异常的胎儿。我们还报告了一个从轻度受影响的父母那里继承了致病性变异的个体。结论 我们的工作对 KAT6B 疾病的基因型和表型谱进行了全面审查和扩展，这将有助于临床医生评估、咨询和管理受影响的个体。四个人在产前增加了颈部半透明/囊性湿疹，两个胎儿患有严重的肾脏异常导致肾功能衰竭。我们还报告了一个从轻度受影响的父母那里继承了致病性变异的个体。结论 我们的工作对 KAT6B 疾病的基因型和表型谱进行了全面审查和扩展，这将有助于临床医生评估、咨询和管理受影响的个体。四个人在产前增加了颈部半透明/囊性湿疹，两个胎儿患有严重的肾脏异常导致肾功能衰竭。我们还报告了一个从轻度受影响的父母那里继承了致病性变异的个体。结论 我们的工作对 KAT6B 疾病的基因型和表型谱进行了全面审查和扩展，这将有助于临床医生评估、咨询和管理受影响的个体。