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Genetics in Medicine : Official Journal... Jan 2012Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal... (Review)
Review
Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype. Sleep abnormalities and scoliosis are common. Growth hormone insufficiency is frequent, and replacement therapy provides improvement in growth, body composition, and physical attributes. Management is otherwise largely supportive. Consensus clinical diagnostic criteria exist, but diagnosis should be confirmed through genetic testing. Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%). Parent-specific DNA methylation analysis will detect >99% of individuals. However, additional genetic studies are necessary to identify the molecular class. There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. Sibling recurrence risk is typically <1%, but higher risks may pertain in certain cases. Prenatal diagnosis is available.
Topics: Diagnosis, Differential; Genetic Association Studies; Genetic Counseling; Genetic Testing; Humans; Morbidity; Prader-Willi Syndrome
PubMed: 22237428
DOI: 10.1038/gim.0b013e31822bead0 -
Sports Medicine (Auckland, N.Z.) Sep 2013Short stature and later maturation of youth artistic gymnasts are often attributed to the effects of intensive training from a young age. Given limitations of available... (Review)
Review
Short stature and later maturation of youth artistic gymnasts are often attributed to the effects of intensive training from a young age. Given limitations of available data, inadequate specification of training, failure to consider other factors affecting growth and maturation, and failure to address epidemiological criteria for causality, it has not been possible thus far to establish cause-effect relationships between training and the growth and maturation of young artistic gymnasts. In response to this ongoing debate, the Scientific Commission of the International Gymnastics Federation (FIG) convened a committee to review the current literature and address four questions: (1) Is there a negative effect of training on attained adult stature? (2) Is there a negative effect of training on growth of body segments? (3) Does training attenuate pubertal growth and maturation, specifically, the rate of growth and/or the timing and tempo of maturation? (4) Does training negatively influence the endocrine system, specifically hormones related to growth and pubertal maturation? The basic information for the review was derived from the active involvement of committee members in research on normal variation and clinical aspects of growth and maturation, and on the growth and maturation of artistic gymnasts and other youth athletes. The committee was thus thoroughly familiar with the literature on growth and maturation in general and of gymnasts and young athletes. Relevant data were more available for females than males. Youth who persisted in the sport were a highly select sample, who tended to be shorter for chronological age but who had appropriate weight-for-height. Data for secondary sex characteristics, skeletal age and age at peak height velocity indicated later maturation, but the maturity status of gymnasts overlapped the normal range of variability observed in the general population. Gymnasts as a group demonstrated a pattern of growth and maturation similar to that observed among short-, normal-, late-maturing individuals who were not athletes. Evidence for endocrine changes in gymnasts was inadequate for inferences relative to potential training effects. Allowing for noted limitations, the following conclusions were deemed acceptable: (1) Adult height or near adult height of female and male artistic gymnasts is not compromised by intensive gymnastics training. (2) Gymnastics training does not appear to attenuate growth of upper (sitting height) or lower (legs) body segment lengths. (3) Gymnastics training does not appear to attenuate pubertal growth and maturation, neither rate of growth nor the timing and tempo of the growth spurt. (4) Available data are inadequate to address the issue of intensive gymnastics training and alterations within the endocrine system.
Topics: Adolescent; Adolescent Development; Body Height; Body Weight; Child; Child Development; Female; Gymnastics; Hormones; Humans; Lower Extremity; Male; Nutritional Status; Physical Conditioning, Human; Physical Exertion; Puberty; Sexual Maturation; Torso
PubMed: 23743792
DOI: 10.1007/s40279-013-0058-5 -
Endocrine Reviews Sep 2022Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the... (Review)
Review
Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at "the child with delayed puberty of uncertain etiology" risk being misapplied to older adolescents likely to have permanent hypogonadism.
Topics: Adolescent; Child; Female; Gonadotropins; Humans; Hypogonadism; Male; Puberty; Puberty, Delayed; Testosterone
PubMed: 34864951
DOI: 10.1210/endrev/bnab043 -
The Angle Orthodontist Mar 2021To evaluate whether the success of miniscrew-assisted rapid palatal expansion (MARPE), performed in patients with advanced bone maturation is related to factors such as...
OBJECTIVES
To evaluate whether the success of miniscrew-assisted rapid palatal expansion (MARPE), performed in patients with advanced bone maturation is related to factors such as midpalatal suture (MPS) maturation, age, sex, or bicortical mini-implant anchorage.
MATERIALS AND METHODS
Twenty-eight cone beam computed tomography (CBCT) scans of adults and post-pubertal adolescents treated by MARPE were included in the sample. CBCT images before (T0) and after expansion (T1) were used to evaluate the skeletal changes and the success or failure of MARPE. Axial images of MPS were extracted from T0 and classified into one of the five maturation stages. The correlation between MARPE success and the factors of age, sex, MPS maturation, and bicortical mini-implant anchorage was investigated.
RESULTS
Only the age showed a statistically significant negative correlation with MARPE success and all the skeletal measures. There was an 83.3% success rate among individuals aged 15 to 19 years, 81.8% from 20 to 29 years, and 20% from 30 to 37 years. MPS maturation showed a negative correlation with the expansion effect. Subjects with stages B or C of MPS maturation showed a 100% success rate, followed by stage D (62.5%) and stage E (58.3%).
CONCLUSIONS
As age increased, there was a decrease in MARPE success and the skeletal effects of maxillary expansion. Sex and bicortical mini-implant anchorage were not shown to be relevant factors. There was no correlation between MPS maturation and MARPE success; however, it was observed that all cases of MARPE failure were classified as stage D or E of MPS maturation.
Topics: Adolescent; Adult; Cone-Beam Computed Tomography; Cranial Sutures; Humans; Maxilla; Palatal Expansion Technique; Palate; Young Adult
PubMed: 33351888
DOI: 10.2319/051420-436.1 -
Endocrine Reviews Jan 2024Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone... (Review)
Review
Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone (GnRH) neuronal activity and pulsatile GnRH secretion. Their critical role in reproductive health was first identified after inactivating variants in genes encoding for KP or NKB signaling were shown to result in congenital hypogonadotropic hypogonadism and a failure of pubertal development. Over the past 2 decades since their discovery, a wealth of evidence from both basic and translational research has laid the foundation for potential therapeutic applications. Beyond KP's function in the hypothalamus, it is also expressed in the placenta, liver, pancreas, adipose tissue, bone, and limbic regions, giving rise to several avenues of research for use in the diagnosis and treatment of pregnancy, metabolic, liver, bone, and behavioral disorders. The role played by NKB in stimulating the hypothalamic thermoregulatory center to mediate menopausal hot flashes has led to the development of medications that antagonize its action as a novel nonsteroidal therapeutic agent for this indication. Furthermore, the ability of NKB antagonism to partially suppress (but not abolish) the reproductive endocrine axis has supported its potential use for the treatment of various reproductive disorders including polycystic ovary syndrome, uterine fibroids, and endometriosis. This review will provide a comprehensive up-to-date overview of the preclinical and clinical data that have paved the way for the development of diagnostic and therapeutic applications of KP and NKB.
Topics: Pregnancy; Female; Humans; Neurokinin B; Kisspeptins; Gonadotropin-Releasing Hormone; Reproduction; Hypothalamus
PubMed: 37467734
DOI: 10.1210/endrev/bnad023 -
Cell Reports. Medicine Nov 2022Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone...
Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr mice. Of note, this gene therapy partially recovers sexual development, substantially restores spermatogenesis, and effectively produces fertile offspring. Furthermore, these favorable effects can be reproduced in adult Lhcgr mice. Our proof-of-concept experiments in the mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with LCF.
Topics: Male; Mice; Animals; Leydig Cells; Receptors, LH; Dependovirus; Chorionic Gonadotropin; Testosterone; Fertility; Disease Models, Animal; Genetic Therapy
PubMed: 36270285
DOI: 10.1016/j.xcrm.2022.100792