Gonadal Function and Testicular Histology in Noonan's Syndrome with Bilateral Cryptorchidism

Sasagawa, Isoji; Nakada, Teruhiro; Kubota, Yōko; Sawamura, T.; Tateno, T.; Ishigooka, Manabu

doi:10.3109/01485019408987778

Cited by 22 publications

(7 citation statements)

References 15 publications

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“…In the literature, histological analyses of testes performed in few NS patients, all of them with cryptorchidism, mostly found interstitial fibrosis associated with abnormalities of the seminiferous tubules (i.e. reduction of tubular diameter, Leydig cells per seminiferous tubules, and spermatogonia per tubule) (34,35). To our knowledge, semen analysis was reported once with low sperm count in one NS male (8).…”

Section: Discussionmentioning

confidence: 88%

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency

Moniez

Pienkowski

Lepage

et al. 2018

European Journal of Endocrinology

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Context: Abnormalities in the hypothalamo-pituitary-gonadal axis have long been reported in Noonan syndrome (NS) males with only few data available in prepubertal children.Objective: The aim of this study was to describe the gonadal function of NS males from childhood to adulthood. Design: It is a retrospective chart review. Patients and methods: A total of 37 males with a genetically confirmed diagnosis of NS were included. Clinical and genetic features, as well as serum hormone levels (LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B) were analysed. Results: Of the 37 patients, 16 (43%) children had entered puberty at a median age of 13.5 years (range: 11.4-15.0 years); age at pubertal onset was negatively correlated with BMI SDS (r = −0.541; P = 0.022). In pubertal boys, testosterone levels were normal suggesting a normal Leydig cell function. In contrast, NS patients had significant lower levels of AMH (mean SDS: −0.6 ± 1.1; P = 0.003) and inhibin B (mean SDS: −1.1 ± 1.2; P < 0.001) compared with the general population, suggesting a Sertoli cell dysfunction. Lower AMH and inhibin B levels were found in NS-PTPN11 patients, whereas these markers did not differ from healthy children in SOS1 patients. No difference was found between cryptorchid and non-cryptorchid patients for AMH and inhibin B levels (P = 0.43 and 0.62 respectively). Four NS-PTPN11 patients had a severe primary hypogonadism with azoospermia/cryptozoospermia. Conclusions: NS males display Sertoli cell-specific primary testicular insufficiency, whereas Leydig cell function seems to be unaffected.

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Section: Discussionmentioning

confidence: 88%

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency

Moniez

Pienkowski

Lepage

et al. 2018

European Journal of Endocrinology

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“…GHD appears to be both more common and more severe in NSLH1 than in NS (Malaquias et al, ; Mazzanti et al, ; Tamburrino et al, ). Other hormonal deficiencies, such as primary hypothyroidism secondary to thyroiditis occasionally occur in both disorders (Ross & Shenkman, ; Sasagawa et al, ; Tamburrino et al, ; Zavras et al, ).…”

Section: Introductionmentioning

confidence: 99%

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

Couser

Keelean‐Fuller

Davenport

et al. 2018

American J of Med Genetics Pt A

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Noonan syndrome (NS), the most common of the RASopathies, is a developmental disorder caused by heterozygous germline mutations in genes encoding proteins in the RAS‐MAPK signaling pathway. Noonan‐like syndrome with loose anagen hair (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by typical features of NS with additional findings of macrocephaly, loose anagen hair, growth hormone deficiency in some, and a higher incidence of intellectual disability. All NSLH1 reported cases to date have had an SHOC2 c.4A>G, p.Ser2Gly mutation; NSLH2 cases have been reported with a PPP1CB c.146G>C, p.Pro49Arg mutation, or c.166G>C, p.Ala56Pro mutation. True cleft palate does not appear to have been previously reported in individuals with NS or with NSLH. While some patients with NS have had growth hormone deficiency (GHD), other endocrine abnormalities are only rarely documented. We present a female patient with NSLH1 who was born with a posterior cleft palate, micrognathia, and mild hypotonia. Other findings in her childhood and young adulthood years include hearing loss, strabismus, and hypopituitarism with growth hormone, thyroid stimulating hormone (TSH), and gonadotropin deficiencies. The SHOC2 mutation may be responsible for this patient's additional features of cleft palate and hypopituitarism.

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“…Cryptorchid testes in boys with Noonan's syndrome have demonstrated only hypoplastic tubules and interstitial fibrosis [32,33]. They also had small penises, a feature that is sometimes reported in cases of Noonan's syndrome and that was likely a secondary effect of decreased testicular production of testosterone.…”

Section: Discussionmentioning

confidence: 96%

“…The infants in our 2 male cases (involving fusion of genital folds and no internal female organs) did not have the PTPN11 mutation, but they did have abnormal testes with both ovarian and gonadoblastoma-like features. Cryptorchid testes in boys with Noonan's syndrome have demonstrated only hypoplastic tubules and interstitial fibrosis [32,33]. They also had small penises, a feature that is sometimes reported in cases of Noonan's syndrome and that was likely a secondary effect of decreased testicular production of testosterone.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Autopsy Findings in Three Cases of Jugular Lymphatic Obstruction Sequence and Cardiac Polyvalvular Dysplasia

Bendon

Asamoah

2008

Pediatr Dev Pathol

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Three infants with a prenatal diagnosis of Noonan's syndrome suffered fetal hydrops and immediate neonatal death. The infants all had the external appearance of jugular lymphatic obstruction sequence with wide-spaced nipples, redundant posterior nuchal skin, and edema of the dorsa of the feet and hands. All 3 demonstrated thick, redundant leaflets of all 4 cardiac valves, and 2 had a membranous ventricular septal defect. One female infant had a mutation of the PTPN11 gene. Two males had no common mutation of PTPN11. The males demonstrated other abnormalities in common, including small penis, testicular malformation, rosette-like appearance of the pituicytes, and an eosinophil infiltration of the pancreatic islets with islet cell hypertrophy. Detailed anatomy of cases of lymphatic obstruction sequence fetuses can be correlated with an increasing number of genetic mutations associated with Noonan's syndrome and related syndromes in mice and humans.

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Gonadal Function and Testicular Histology in Noonan's Syndrome with Bilateral Cryptorchidism

Cited by 22 publications

References 15 publications

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency

Noonan syndrome males display Sertoli cell-specific primary testicular insufficiency

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

Perinatal Autopsy Findings in Three Cases of Jugular Lymphatic Obstruction Sequence and Cardiac Polyvalvular Dysplasia

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