Kodytková Aneta, Dušátková Petra, Amaratunga Shenali Anne, Koloušková Stanislava, Obermannová Barbora, Pomahačová Renata, Průhová Štěpánka, Šnajderová Marta, Šumník Zdeněk, Zapletalová Jiřina, Semjonov Valerij, Lebl Jan
Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia.
Department of Pediatrics, Faculty of Medicine, Charles University and University Hospital Pilsen, Pilsen, Czechia.
Front Endocrinol (Lausanne). 2025 Apr 15;16:1527140. doi: 10.3389/fendo.2025.1527140. eCollection 2025.
Prader-Willi syndrome (PWS) is primarily caused by a paternal microdeletion of the 15q11-q13 region, maternal uniparental disomy (mUPD) or unbalanced translocations. The gene, located within 15q11-q13, is a master regulator of pubertal initiation. We aimed to compare variant pubertal onset and progression with recent normative data and to correlate it with abnormal gene status.
Age at pubarche, gonadarche, subsequent pubertal progression and bone age (BA) at gonadarche were investigated in 37 PWS patients (18 females) who already entered pubarche and/or gonadarche with median age 11.1 (95% CI: 6.4 - 18.8) years. All patients were re-tested to confirm genetic subtypes of PWS. The gene was analyzed using single gene sequencing.
Out of 37 subjects, 22 had microdeletion and 15 mUPD. Regardless of genetic subtypes and gene status, no correlation between genotypes and the pubertal pattern was found. They initiated pubarche early - girls at 7.4 (95%CI:6.4-8.4), and boys at 9.2 (8.2-10.2) years. The subsequent progression from PH2 to PH4 (pubic hair development) was prolonged to 3.7 years in girls (1.5-5.9;p<0.05), and 2.9 in boys (2.2-3.6;p<0.001). The age at gonadarche was adequate - 10.0 years in girls (8.8-11.2), and 11.0 in boys (9.8-12.1). Progression rate of breast development from B2 to B4 was 3.9 (0.2-7.5) years in girls and of testicular volume from 4 ml to 15ml was 3.8 (0.0-8.1) years in boys. The BA at gonadarche is advanced by 0.6 ± 1.1 years (p<0.001).
Children with PWS, regardless of the genetic subtype and/or status, had an early pubarche and normally timed gonadarche. Pubarche progression was slower. Advanced BA was significantly correlated with gonadarche.
普拉德-威利综合征（PWS）主要由父源15q11-q13区域的微缺失、母源单亲二倍体（mUPD）或不平衡易位引起。位于15q11-q13内的基因是青春期启动的主要调节因子。我们旨在将青春期启动和进展的变异与近期的标准数据进行比较，并将其与异常的基因状态相关联。
对37例已进入青春期和/或性腺发育青春期的普拉德-威利综合征患者（18例女性）进行了研究，调查了阴毛初现、性腺发育青春期的年龄、随后的青春期进展以及性腺发育青春期时的骨龄（BA），患者中位年龄为11.1岁（95%可信区间：6.4 - 18.8岁）。对所有患者进行重新检测以确认普拉德-威利综合征的基因亚型。使用单基因测序分析该基因。
37名受试者中，22例有微缺失，15例有mUPD。无论基因亚型和基因状态如何，均未发现基因型与青春期模式之间存在相关性。他们阴毛初现较早——女孩为7.4岁（95%可信区间：6.4 - 8.4岁），男孩为9.2岁（8.2 - 10.2岁）。从PH2到PH4（阴毛发育）的后续进展在女孩中延长至3.7年（1.5 - 5.9年；p<0.05），在男孩中为2.9年（2.2 - 3.6年；p<0.001）。性腺发育青春期的年龄正常——女孩为10.0岁（8.8 - 11.2岁），男孩为11.0岁（9.8 - 12.1岁）。女孩从B2到B4的乳房发育进展率为3.9年（0.2 - 7.5年），男孩睾丸体积从4毫升增加到15毫升的进展率为3.8年（0.0 - 8.1年）。性腺发育青春期时的骨龄提前0.6±1.1岁（p<0.001）。
普拉德-威利综合征患儿，无论基因亚型和/或状态如何，阴毛初现较早，性腺发育青春期时间正常。阴毛发育进展较慢。骨龄提前与性腺发育青春期显著相关。
