Genital tract function in men with Noonan syndrome.

Elsawi, M.; Pryor, J. P.; Klufio, G; Barnes, Carol A.; Patton, Michael A.

doi:10.1136/jmg.31.6.468

Cited by 59 publications

(32 citation statements)

References 10 publications

(4 reference statements)

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“…Increased luteinizing hormon (LH) and follicle stimulating hormone (FSH) levels are present in prepubertal boys [14]. High FSH levels and poor quality semen have been found in adults, suggesting a failure of spermatogenesis in patients with testicular maldescent [15]. In both sexes, pubertal development is delayed.…”

Section: Clinical Descriptionmentioning

confidence: 99%

Noonan syndrome

Burgt

2007

Orphanet J Rare Dis

302

222

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Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set posteriorly rotated ears with a thickened helix. The cardiovascular defects most commonly associated with this condition are pulmonary stenosis and hypertrophic cardiomyopathy. Other associated features are webbed neck, chest deformity, mild intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency and lymphatic dysplasias. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Recently, mutations in the KRAS gene have been identified in a small proportion of patients with NS. A DNA test for mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. NS should be considered in all foetuses with polyhydramnion, pleural effusions, oedema and increased nuchal fluid with a normal karyotype. With special care and counselling, the majority of children with NS will grow up and function normally in the adult world. Management should address feeding problems in early childhood, evaluation of cardiac function and assessment of growth and motor development. Physiotherapy and/or speech therapy should be offered if indicated. A complete eye examination and hearing evaluation should be performed during the first few years of schooling. Preoperative coagulation studies are indicated. Signs and symptoms lessen with age and most adults with NS do not require special medical care.

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Section: Clinical Descriptionmentioning

confidence: 99%

Noonan syndrome

Burgt

2007

Orphanet J Rare Dis

302

222

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“…UT are associated with impaired fertility (6,7). A small number of males with NS have had assessment of gonadal function in prepubertal period (2) as well as adulthood (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study

Ankarberg‐Lindgren¹,

Westphal²,

Dahlgren³

2011

European Journal of Endocrinology

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Objective: To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS). Design: In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population. Methods: Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer. Results: Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E 2 ) concentrations started to increase during puberty and inhibin B and anti-Mü llerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P!0.01), FSH (7.1 vs 2.5 U/l, P!0.001), testosterone (18.7 vs 15.6 nmol/l, P!0.01) and E 2 (66 vs 46 pmol/l, P!0.001) levels and lower AMH (33 vs 65 pmol/l, P!0.01) and inhibin B (median 108 vs 187 pg/ml, P!0.01) levels than the reference population. Conclusions: In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.

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“…On this basis, and despite anecdotal reports to the contrary, it would be expected that impaired gonadal function in NS boys might reasonably be associated more with primary gonadal dysfunction than central hypothalamo-pituitary-gonadal axis disturbance. In general, this is borne out by other anecdotal and small-scale study reports [4,5,6,7,8,9,10] (table 1) and, in particular, with high basal FSH levels suggesting a disturbance in Sertoli cell function resulting in hypergonadotrophic hypogonadism.…”

Section: Gonadal Axis In Nsmentioning

confidence: 88%

Noonan Syndrome: The Hypothalamo-Adrenal and Hypothalamo-Gonadal Axes

Kelnar¹

2009

Horm Res Paediatr

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The hypothalamo-pituitary-adrenal axis has not been studied systematically in Noonan syndrome (NS), despite potential concerns about other aspects of hypothalamo-pituitary function. While adrenarche may be delayed in children with constitutional growth of puberty and in isolated GH deficiency, this does not generally seem to be the case in hypergonadotrophic hypogonadism due to Turner syndrome (TS) and this is (anecdotally) the usual hormonal profile in NS children and adults. Precocious or ‘exaggerated’ adrenarche can be associated with intrauterine growth retardation and is a forerunner of syndrome X. Although NS neonates often have ‘normal’ birth weights, in some it can be artificially inflated by subcutaneous edema (as in TS, where intrauterine growth retardation is characteristic). Overall, however, a controlling role for adrenarche (whether precocious or delayed) in gonadarche in NS seems unlikely. Neither normally descended testes nor normal (even if delayed) pubertal development implies normal fertility in NS men. Interactions between fetal, neonatal, childhood and pubertal testis development and gonadal axis maturation are complex. There is probably a spectrum of abnormalities in NS, but most commonly primary gonadal failure and hypergonadotrophic hypogonadism – characteristic NS molecular genetic abnormalities – may be important for normal germ cell proliferation, development and migration. The identification of different gene defects facilitates understanding of NS phenotypic diversity and provides opportunities for prospective studies on gonadal and adrenal axes in better defined populations less subject to ascertainment bias. At a clinical level, more longitudinal data are still needed with regard to the natural history of pubertal timing, its tempo of progression and the pattern of pubertal growth.

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Genital tract function in men with Noonan syndrome.

Cited by 59 publications

References 10 publications

Noonan syndrome

Noonan syndrome

Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study

Noonan Syndrome: The Hypothalamo-Adrenal and Hypothalamo-Gonadal Axes

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