Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche

被引:0
作者
Kodytkova, Aneta [1 ,2 ]
Dusatkova, Petra [1 ,2 ]
Amaratunga, Shenali Anne [1 ,2 ]
Kolouskova, Stanislava [1 ,2 ]
Obermannova, Barbora [1 ,2 ]
Pomahacova, Renata [3 ,4 ]
Pruhova, Stepanka [1 ,2 ]
Snajderova, Marta [1 ,2 ]
Sumnik, Zdenek [1 ,2 ]
Zapletalova, Jirina [5 ,6 ]
Semjonov, Valerij [7 ]
Lebl, Jan [1 ,2 ]
机构
[1] Charles Univ Prague, Fac Med 2, Dept Pediat, Prague, Czech Republic
[2] Motol Univ Hosp, Prague, Czech Republic
[3] Charles Univ Prague, Fac Med, Dept Pediat, Plzen, Czech Republic
[4] Univ Hosp Plzen, Plzen, Czech Republic
[5] Palacky Univ, Fac Med, Dept Pediat, Olomouc, Czech Republic
[6] Olomouc Univ Hosp, Olomouc, Czech Republic
[7] Motol Univ Hosp, Dept Stat, Prague, Czech Republic
来源
FRONTIERS IN ENDOCRINOLOGY | 2025年 / 16卷
关键词
Prader-Willi syndrome puberty; pubarche; gonadarche; MKRN3; gene; puberty; bone age; CENTRAL PRECOCIOUS PUBERTY; PREMATURE ADRENARCHE; MKRN3; LEVELS; CHILDREN; HYPOGONADISM; ADVANCEMENT; DELETIONS; DECLINE; PATTERN; OBESITY;
D O I
10.3389/fendo.2025.1527140
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction Prader-Willi syndrome (PWS) is primarily caused by a paternal microdeletion of the 15q11-q13 region, maternal uniparental disomy (mUPD) or unbalanced translocations. The MKRN3 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 MKRN3 gene status. Methods 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 MKRN3 gene was analyzed using single gene sequencing. Results Out of 37 subjects, 22 had microdeletion and 15 mUPD. Regardless of genetic subtypes and MKRN3 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). Conclusions Children with PWS, regardless of the genetic subtype and/or MKRN3 status, had an early pubarche and normally timed gonadarche. Pubarche progression was slower. Advanced BA was significantly correlated with gonadarche.
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