China
Africa
Explore chapters and articles related to this topic
Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
Affected males may display a wide range of behavioral and cognitive manifestations, but they are never asymptomatic [23]. The behavioral phenotype is characterized by autism spectrum behaviors such as attention deficit/hyperactivity, expressive delay, tactile defensiveness, perseverative speech, and echolalia, as well as social anxiety and avoidance of eye contact. The cognitive phenotype generally is moderate to severe mental impairment. Ten to twenty percent have seizures. Physical characteristics are more readily identifiable around or after puberty. These findings are similar to a connective tissue disorder, including hyperextensible joints; soft, smooth skin; flat feet; and mitral valve prolapse. The facial appearance is often described as long and narrow with prognathism and large ears. Macrocephaly may also be present. Most develop macroorchidism [25].
Fragile X and X-linked Mental Retardation
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Jacquemont Sebastien, Hagerman Randi, des Portes Vincent
Macroorchidism is one of the most consistent findings (over 80% of the adult cases), but it is not usually seen in young children. By the age of 14 years old, 90% of the boys have testicular measurements above the 95th percentile (10). The endocrine function has been investigated in order to understand the mechanism underlying macroorchidism. Mild elevations of gonadotropin levels have been reported (11,12), suggesting a hypothalamo-pituitary dysfunction. A small subgroup of patients with FXS present with a Prader–Willi syndrome (PWS) phenotype including extreme obesity, short stature, small extremities, and hypogonadism (13-15). It is likely that this subgroup represents a more severe form of hypothalamic dysfunction. It is recommended to test for fragile X in patients presenting with obesity or other PWS features and developmental delay.
Primary Pituitary Disease
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Christopher M. Jones, John Ayuk
Clinical features FSH-secreting pituitary adenomas are usually asymptomatic. Clinical features in male patients generally relate to tumour mass effect and the development of hypogonadism. An association between FSHoma and macroorchidism has also been reported, particularly in prepubertal males.71 Development of an FSHoma in a premenopausal woman can result in ovarian hyperstimulation syndrome. This manifests as abdominal bloating secondary to increased ovarian size or the accumulation of ascites. FSH-secreting adenomas arising in postmenopausal women are invariably asymptomatic and present a significant diagnostic challenge.
Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic LHCGR Gene Mutation
Published in Endocrine Research, 2020
A. Daussac, P. Barat, N. Servant, M. Yacoub, S. Missonier, F Lavran, L. Gaspari, C. Sultan, F. Paris
A number of studies have shown that constitutive activation of the signal transduction pathway of G protein-coupled receptor as a result of mutations of either the receptor or the G protein may lead to autonomous endocrine function. The sporadic activating mutation of Gsα, which inhibits the intrinsic GTPase activity, activates adenylcyclase in a receptor-independent way, giving rise to the various autonomous endocrine hyperfunctions usually found in McCune-Albright syndrome (MAS).22 Testicular function is frequently disrupted in MAS, with PPP in about 20% of cases, as well as Sertoli cell hyperplasia, which is responsible for macroorchidism.33–35 For our patient, molecular study of the Gsα gene revealed no mutation.
Pediatric pituitary adenoma with mixed FSH and TSH immunostaining and FSH hypersecretion in a 6 year-old girl with precocious puberty: case report and multidisciplinary management
Published in International Journal of Neuroscience, 2022
Marco Ceraudo, Diego Criminelli Rossi, Natascia Di Iorgi, Armando Cama, Gianluca Piatelli, Alessandro Consales
Similar cases were reported by Clemente et al. [16], that have described two cases of pure FSH-secreting pituitary adenoma. The first case reported was a 12-year-old boy with macroorchidism due to a pituitary microadenoma, probably FSH-secreting, treated with medical therapy and followed radiologically, while the second case was a 15-year-old boy with panhypopituitarism due to an FSH-producing macroadenoma that underwent transsphenoidal surgery. Only one case of TSH-FSH secreting pituitary adenoma has been reported in the literature by Vargas et al. [20]. The authors reported a case of a 19-year-old young women with a medical history of hyperthyroidism, precocious puberty and ovarian hyperstimulation in childhood (treated with bilateral oophorectomy and oral contraceptives). The patient was affected by a pituitary macroadenoma that was misdiagnosed for ten years before it was identified with the occurrence of hyperthyroidism symptoms. She successfully underwent transsphenoidal resection of the pituitary macroadenoma with resolution of the symptoms due to hyperthyroidism and mass effect. However, there are differences between the three cases and ours. Indeed, the first case of Clemente et al. [16] presented clinical signs and symptoms of FSH hypersecretion, but information about histopathological examinations lacks, while the second case presented panhypopituitarism due to macroadenoma compression, but no clinical expression of FSH hypersecretion. The case report by Vargas et al. [20] is a description of the natural history of this kind of tumor during childhood and adolescence. The patient was treated when she was 19, but her clinical conditions were probably due the excessive secretion of FSH and TSH [20]. Misdiagnosis leads to inappropriate treatment (i.e. bilateral oophorectomy) and/or delayed diagnosis, and these tumors often exhibit progressive growth and invasiveness [6]. Furthermore, in all the previous cases [16,20] diagnosis of pituitary adenoma has been done in adolescence, during the pubertal stage. In our case, pituitary adenoma was diagnosed in a pre-pubertal stage few months after the onset of symptoms and treated with surgical and medical therapy. The timing of diagnosis and the treatment of these tumors, related to pre-pubertal or pubertal stage, are crucial for the growth outcome of these patients.
Platelets as a surrogate disease model of neurodevelopmental disorders: Insights from Fragile X Syndrome
Published in Platelets, 2018
David Pellerin, Audrey Lortie, François Corbin
Fragile X Syndrome is the leading inherited monogenic cause of ID and ASD, affecting approximately 1 in 4,000 males and 1 in 8,000 females [23]. The clinical phenotype is further characterized by a wide array of behavioral, neuropsychiatric and physical characteristics, such as epilepsy, attention deficit hyperactivity disorder, macroorchidism and connective tissue anomalies (i.e., hyper-extendible joints, flat feet, high-arched palate) [1,24]. About 30% of FXS males meet diagnostic criteria for ASD and among those who do not, 90% present autistic features [25,26]. Almost all cases of FXS (>98%) result from the absence of expression of the fragile X mental retardation protein (FMRP) caused by a CGG trinucleotide-repeat expansion in the 5ʹ-untranslated region of the fragile X mental retardation 1 (FMR1) gene along with the methylation of its promoter [27,28]. Aside from cardiac and skeletal striated muscles, FMRP expression has been described in all investigated tissues [29], including megakaryocytes [30] and platelets [31]. FMRP is an RNA-binding protein having well-known RNA-binding motifs, one RGG-box and two KH domains [32], and is involved in transport and translation regulation of mRNAs. In fact, 95% of FMRP is normally associated with polyribosomes in mouse brain tissue [33] and in human HeLa [34] and megakaryoblastic MEG-01 [30] cells, but not in human platelets [31]. In brain neurons, FMRP specifically binds nearly 4% of all mRNAs [35] and plays a crucial role in local activity-dependent synaptic protein synthesis by acting chiefly as a translational repressor of its target mRNAs through ribosomal translocation stalling [36]. Many of these target mRNAs encode essential synaptic plasticity-related and translational control signaling pathways proteins, some of which have also been associated with increased risk of ASD (e.g., PTEN, TSC2, neurexin1) [37]. This FMRP-controlled protein synthesis is further thought to underlie learning, memory, and behavioral modulation owing to its involvement in synaptogenesis and long-term plasticity [35,38–40]. FMRP lies at the crossroads of the two major translational control signaling cascades downstream of group 1 (Gp1) metabotropic glutamate receptors (mGluR1 and mGluR5), that is the mitogen-activated protein kinase—extracellular signal-regulated kinase (MAPK/ERK) and the phosphoinositide 3-kinase—Akt—mammalian target of rapamycin (PI3K/Akt/mTOR) pathways (Figure 1A). FMRP normally works by functionally opposing the pro-translational effects of the Gp1 mGluR signaling network [41]. The synaptic stimulation of Gp1 mGluR therefore culminates in facilitation of translation, which in turn facilitates long-term depression (LTD) plasticity via post-synaptic AMPA receptors endocytosis [42,43].