Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche
IntroductionPrader-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 pubert...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1527140/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850200386724429824 |
|---|---|
| author | Aneta Kodytková Petra Dušátková Shenali Anne Amaratunga Stanislava Koloušková Barbora Obermannová Renata Pomahačová Štěpánka Průhová Marta Šnajderová Zdeněk Šumník Jiřina Zapletalová Valerij Semjonov Jan Lebl |
| author_facet | Aneta Kodytková Petra Dušátková Shenali Anne Amaratunga Stanislava Koloušková Barbora Obermannová Renata Pomahačová Štěpánka Průhová Marta Šnajderová Zdeněk Šumník Jiřina Zapletalová Valerij Semjonov Jan Lebl |
| author_sort | Aneta Kodytková |
| collection | DOAJ |
| description | IntroductionPrader-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.MethodsAge 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.ResultsOut 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).ConclusionsChildren 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. |
| format | Article |
| id | doaj-art-39c9d3d1d5b142f0b6294a202878b2cf |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-39c9d3d1d5b142f0b6294a202878b2cf2025-08-20T02:12:20ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15271401527140Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarcheAneta Kodytková0Petra Dušátková1Shenali Anne Amaratunga2Stanislava Koloušková3Barbora Obermannová4Renata Pomahačová5Štěpánka Průhová6Marta Šnajderová7Zdeněk Šumník8Jiřina Zapletalová9Valerij Semjonov10Jan Lebl11Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, Faculty of Medicine, Charles University and University Hospital Pilsen, Pilsen, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, Faculty of Medicine, Palacky University and Olomouc University Hospital, Olomouc, CzechiaDepartment of Statistics, Motol University Hospital, Prague, CzechiaDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, CzechiaIntroductionPrader-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.MethodsAge 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.ResultsOut 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).ConclusionsChildren 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1527140/fullPrader-Willi syndrome pubertypubarchegonadarcheMKRN3 genepubertybone age |
| spellingShingle | Aneta Kodytková Petra Dušátková Shenali Anne Amaratunga Stanislava Koloušková Barbora Obermannová Renata Pomahačová Štěpánka Průhová Marta Šnajderová Zdeněk Šumník Jiřina Zapletalová Valerij Semjonov Jan Lebl Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche Frontiers in Endocrinology Prader-Willi syndrome puberty pubarche gonadarche MKRN3 gene puberty bone age |
| title | Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche |
| title_full | Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche |
| title_fullStr | Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche |
| title_full_unstemmed | Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche |
| title_short | Variant pubertal development in Prader-Willi syndrome: early and slow progression of pubarche with normal age at gonadarche |
| title_sort | variant pubertal development in prader willi syndrome early and slow progression of pubarche with normal age at gonadarche |
| topic | Prader-Willi syndrome puberty pubarche gonadarche MKRN3 gene puberty bone age |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1527140/full |
| work_keys_str_mv | AT anetakodytkova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT petradusatkova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT shenalianneamaratunga variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT stanislavakolouskova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT barboraobermannova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT renatapomahacova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT stepankapruhova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT martasnajderova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT zdeneksumnik variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT jirinazapletalova variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT valerijsemjonov variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche AT janlebl variantpubertaldevelopmentinpraderwillisyndromeearlyandslowprogressionofpubarchewithnormalageatgonadarche |