The Experts below are selected from a list of 5262 Experts worldwide ranked by ideXlab platform
Moshe Phillip - One of the best experts on this subject based on the ideXlab platform.
-
Familial central Precocious Puberty suggests autosomal dominant inheritance
2020Co-Authors: Liat De Vries, Arieh Kauschansky, Mordechai Shohat, Moshe PhillipAbstract:The prevalence of Precocious Puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial Precocious Puberty and to identify characteristics that distinguish familial from isolated Precocious Puberty. Of the 453 children referred to our center for suspected Precocious Puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central Precocious Puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 ؎ 1.96 vs. 12.66 ؎ 1.18 yr; P ؍ 0.0001) and more advanced Puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P ؍ 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for Precocious Puberty was 0. (1) demonstrated that Puberty may occur at an earlier age than previously thought, with a rate of early Puberty four times higher in African-American girls than in Caucasian girls. This observation suggested a genetic regulation of the timing of Puberty. Some pediatric endocrinologists believe that the pubertal pattern may be influenced by familial trends, such that families with one member with Precocious Puberty have a higher than normal probability of having another. However, scientific support for this assumption remains sparse. We found only a few published descriptions of cases of familial central Precocious Puberty (2-6) and only one study (3) of the prevalence of familial cases in a series of 58 patients with central Precocious Puberty. In the present study, we sought to determine the mode of inheritance of familial Precocious Puberty (FPP) in families with central Precocious Puberty and to identify specific clinical or laboratory features that distinguish familial from sporadic cases. We also calculated the prevalence of FPP at our tertiary care center in a given period of time. Patients and Methods Patients Of the 453 children evaluated in our clinic for Precocious secondary sexual development between January 1, 1997, and December 31, 2000, 156 were found to have idiopathic central Precocious Puberty. The rest presented with Precocious adrenarche (n ϭ 101), early Puberty (n ϭ 89), premature thelarche (n ϭ 58), obesity associated with pseudothelarche (n ϭ 19), and other diagnoses (n ϭ 26); four were lost to follow-up. The diagnosis of Precocious Puberty was based on the presence of secondary sexual characteristics before age 8 yr in females and 9 yr in males. In girls, central Precocious Puberty was diagnosed on the basis of clinical characteristics, including appearance of breast buds before 8 yr of age accompanied by the presence of one or more of the following findings: menses, pubic hair, accelerated growth velocity, or bone age greater than 2 sd above chronological age. When the clinical picture was not obvious, the patients were followed for at least 6 months before the diagnosis was made. Adopted girls were excluded, as were girls with chronic disease, bone dysplasia, organic brain disease, congenital adrenal hyperplasia or other endocrinological abnormalities, and girls who had received radiation therapy and/or chemotherapy. Written informed consent was obtained from all families. The study was approved by the institutional human research committee. Methods At the first visit, the pedigree was determined, detailing medical illnesses and timing of Puberty in family members. The parents completed a structured questionnaire including items on Puberty in first-, second-, and third-degree relatives, and they were asked to contact directly the children's grandparents, aunts, uncles, and cousins to determine the age of Puberty directly from them. We collected the data by contacting the parents by phone. First-degree relatives were defined as mother, father, brother(s), and sister(s); second-degree relatives as grandparents, aunt(s), and uncle(s); and third-degree relatives as cousins. Females were asked about age at appearance of breast buds and age at menarche and males about age at onset of pubertal changes and age at initiation of full-face shaving. Those who met the following criteria were included in the study group of FPP: 1) presentation with gonadotropin-dependent central Precocious Puberty, as described above; and 2) at least one of the following: menarche at age 10 yr or earlier in a first-, second-, or third-degree female relative; clinically documented Precocious Puberty, as described above, in a first-, second-, or third-degree relative; or full Puberty, including full facial shaving, earlier than age 13 yr in a first-, second-, or third-degree male relative. [For Jewish males, age 13 (bar mitzvah) is a significant and well-remembered milestone.] Girls with idiopathic central Precocious Puberty without a family history were considered to have sporadic Precocious Puberty (SPP). All patients underwent clinical, biochemical, and bone age evaluation on admission. Pubertal stage was determined according to Marshall and Abbreviations: BMI, Body mass index; FPP, familial Precocious Puberty; SDS, sd score; SPP, sporadic Precocious Puberty. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community
-
a novel mkrn3 missense mutation causing familial Precocious Puberty
Human Reproduction, 2014Co-Authors: L De Vries, Galia Gatyablonski, N Dror, A Singer, Moshe PhillipAbstract:Central Precocious Puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central Precocious Puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene. A novel missense mutation (p.H420Q) in the imprinted MKRN3 gene was identified in the four affected siblings, in their unaffected father and in his affected mother. An in silico mutant MKRN3 model predicts that the mutation p.H420Q leads to reduced zinc binding and, subsequently, impaired RNA binding. These findings support the fundamental role of the MKRN3 protein in determining pubertal timing.
-
familial central Precocious Puberty suggests autosomal dominant inheritance
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Liat De Vries, Arieh Kauschansky, Mordechai Shohat, Moshe PhillipAbstract:The prevalence of Precocious Puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial Precocious Puberty and to identify characteristics that distinguish familial from isolated Precocious Puberty. Of the 453 children referred to our center for suspected Precocious Puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central Precocious Puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 ± 1.96 vs. 12.66 ± 1.18 yr; P = 0.0001) and more advanced Puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for Precocious Puberty was 0.38 (0.45 after exclusion of young siblings) ...
Ana Claudia Latronico - One of the best experts on this subject based on the ideXlab platform.
-
causes diagnosis and treatment of central Precocious Puberty
The Lancet Diabetes & Endocrinology, 2016Co-Authors: Ana Claudia Latronico, Vinicius Nahime Brito, Jeanclaude CarelAbstract:Summary Central Precocious Puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an inappropriate chronological age (before 8 years in girls and 9 years in boys). It can be attributable to cerebral congenital malformations or acquired insults, but the cause in most cases in girls remains unknown. MKRN3 gene defects have been identified in familial disease, with important basic and clinical results. Indeed, genetic analysis of this gene should be included in the routine clinical investigation of familial and idiopathic cases of central Precocious Puberty. Gonadotropin-releasing hormone agonists are the gold-standard treatment. The assessment and management of this disease remain challenging for paediatric endocrinologists. In this Series paper, we describe current challenges involving the precise diagnosis and adequate treatment of this disorder.
-
a gpr54 activating mutation in a patient with central Precocious Puberty
The New England Journal of Medicine, 2008Co-Authors: Milena Gurgel Teles, Vinicius Nahime Brito, Berenice B Mendonca, Suzy D C Bianco, Ericka B Trarbach, Wendy Kuohung, Stephanie B Seminara, Ursula B Kaiser, Ana Claudia LatronicoAbstract:Gonadotropin-dependent, or central, Precocious Puberty is caused by early maturation of the hypothalamic–pituitary–gonadal axis. In girls, this condition is most often idiopathic. Recently, a G protein–coupled receptor, GPR54, and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). In this study, we have identified an autosomal dominant GPR54 mutation — the substitution of proline for arginine at codon 386 (Arg386Pro) — in an adopted girl with idiopathic central Precocious Puberty (whose biologic family was not available for genetic studies). In vitro studies have shown that this mutation leads to prolonged activation of intracellular signaling pathways in response to kisspeptin. The Arg386Pro mutant appears to be associated with central Precocious Puberty.
-
diagnostic value of fluorometric assays in the evaluation of Precocious Puberty
The Journal of Clinical Endocrinology and Metabolism, 1999Co-Authors: Vinicius Nahime Brito, Ana Claudia Latronico, Ivo J P Arnhold, M C Batista, M F Borges, A C P Thirone, B H Jorge, Maria Beatriz Da Fonte Kohek, Berenice B MendoncaAbstract:To establish normative data and determine the value of fluorometric AutoDELFIA assays (Wallac Oy) in the investigation of Precocious Puberty, we determined serum levels of LH, FSH, testosterone, and estradiol under basal and GnRH-stimulated conditions in 277 normal subjects at various pubertal stages and in 77 patients with Precocious Puberty. A substantial overlap was observed in basal and GnRH-stimulated gonadotropin levels in normal individuals of both sexes with pubertal Tanner stages 1 and 2. The 95th percentile of the normal prepubertal population was the cut-off limit between prepubertal and pubertal levels. These limits were 0.6 IU/L in both sexes for basal LH, 9.6 IU/L in boys and 6.9 IU/L in girls for peak LH after GnRH stimulation, 19 ng/dL in boys for basal testosterone, and 13.6 pg/mL in girls for basal estradiol. Basal and peak LH exceeding these limits were considered positive tests for the diagnosis of gonadotropin-dependent Precocious Puberty. According to these criteria, the sensitivities of basal and peak LH for the latter diagnosis were 71.4% and 100% in boys, and 62.7% and 92.2% in girls. The specificity and positive predicted value were 100% in both sexes for basal and peak LH levels. The negative predicted values for basal and peak LH were 62.5% and 100% in boys, and 40.6% and 76.5% in girls. Basal and GnRH-stimulated FSH levels overlapped among the various pubertal stages in normal subjects and were, in general, not helpful in the differential diagnosis of Precocious Puberty. In conclusion, basal LH levels were sufficient to establish the diagnosis of gonadotropin-dependent Precocious Puberty in 71.4% of boys and 62.7% of girls. In the remaining patients, a GnRH stimulation test was still necessary to confirm this diagnosis. Finally, suppressed LH and FSH levels after GnRH stimulation indicate gonadotropin-independent sexual steroid production.
-
a novel mutation of the luteinizing hormone receptor gene causing male gonadotropin independent Precocious Puberty
The Journal of Clinical Endocrinology and Metabolism, 1995Co-Authors: Ana Claudia Latronico, J N Anasti, Ivo J P Arnhold, Berenice B Mendonca, Sorahia Domenice, M C C Albano, Keith Zachman, B L Wajchenberg, Constantine TsigosAbstract:Familial male-limited Precocious Puberty (FMPP) is an autosomal dominant gonadotropin-independent disorder. Affected males generally develop signs of Precocious Puberty in early childhood. They typically show Leydig cell hyperplasia and increased testosterone production typical for their age, whereas circulating LH concentrations remain prepubertal. Several dominant point mutations of the LH receptor gene were identified in pedigrees with familial male-limited Precocious Puberty and were shown to cosegregate with the disease. Here we report a novel heterozygote point mutation in the LH receptor gene of a Brazilian boy with gonadotropin-independent Precocious Puberty. This mutation substitutes alanine 568 with valine at the carboxyterminus of the third cytosolic loop of the LH receptor. The unoccupied mutant receptors confer constitutive activation of adenyl cyclase activity when expressed in COS-7 cells, resulting in 4-fold higher cAMP concentrations over baseline compared with cells expressing an equival...
Ora H. Pescovitz - One of the best experts on this subject based on the ideXlab platform.
-
treatment of familial male limited Precocious Puberty with bicalutamide and anastrozole
The Journal of Pediatrics, 2006Co-Authors: Nerissa C Kreher, Ora H. Pescovitz, Paul Delameter, Anatoly Tiulpakov, Zeev HochbergAbstract:This report describes the use of bicalutamide and anastrozole in two subjects with familial male-limited Precocious Puberty. Clinical improvements include decreased facial acne and pubic hair. Most importantly, a marked decrease in growth velocity and skeletal advancement has been achieved.
-
tamoxifen treatment for Precocious Puberty in mccune albright syndrome a multicenter trial
The Journal of Pediatrics, 2003Co-Authors: Erica A. Eugster, Stephen D Rubin, Edward O Reiter, Paul V Plourde, Hann Chang Jou, Ora H. PescovitzAbstract:Abstract Objective We undertook a 1-year multicenter trial of tamoxifen treatment for Precocious Puberty in girls with McCune-Albright syndrome (MAS). Study design Girls ≤10 years with classic or atypical MAS were recruited. Pretreatment history was collected for 6 months. Patients received 20 mg tamoxifen daily. Diaries were used to record bleeding. Evaluations included physical examination, bone age, pelvic ultrasound, hormone levels, and safety assessments. Results A total of 28 girls (2.9-10.9 years of age) were enrolled from 20 centers, of whom 25 completed 12 months of tamoxifen treatment. Compared with before the study, vaginal bleeding episodes decreased (3.42±3.36/year vs 1.17±1.41/year), growth velocity slowed (SDS 1.22±2.65 vs −0.59±3.06, P = .005), and rate of bone maturation decreased (1.21±0.78 vs 0.72±0.36, P = .02). Ovarian volumes were enlarged and asymmetric throughout the study, and uterine volumes were increased. No adverse events occurred. Conclusions Tamoxifen treatment of Precocious Puberty in MAS results in a reduction of vaginal bleeding and significant improvements in growth velocity and rate of skeletal maturation.
Hanshilger Ropers - One of the best experts on this subject based on the ideXlab platform.
-
cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male limited Precocious Puberty
Human Molecular Genetics, 1993Co-Authors: H Kremer, Edwin M Mariman, Barto J Otten, George W Moll, Gerard B A Stoellnga, Jan M Wit, Maarten Jansen, Sten L Drop, Brigitte H W Faas, Hanshilger RopersAbstract:Familial male-limited Precocious Puberty is a male-limited autosomal dominant condition. It is characterized by increased testosterone synthesis in the absence of testicular stimulation by luteinizing hormone (LH). We hypothesised that an abnormal configuration of the LH receptor might autonomously activate G protein coupling, and thereby cause the overproduction of testosterone in this condition. To test this hypothesis, we screened for mutations in a part of the LH receptor gene that is important for G protein binding. DNA sequence variation was detected in 2 out of 5 families with male-limited Precocious Puberty by the single strand conformation polymorphism technique. Direct sequencing demonstrated different single nucleotide substitutions in the sixth transmembrane region of the LH receptor gene. The mutations cosegregated with the disorder in both families (lod score 5.76 without recombination). Both mutations cause an amino acid substitution in the sixth transmembrane domain, close to the C-terminal portion of the third cytoplasmatic loop, a region which is important for the binding of G proteins. We conclude that familial male-limited Precocious Puberty cosegregates with missense mutations in the LH receptor gene. These findings support the hypothesis that increased activity of the LH receptor is the pathogenetic mechanism that causes the abnormal pubertal development in this condition.
Zeev Hochberg - One of the best experts on this subject based on the ideXlab platform.
-
treatment of familial male limited Precocious Puberty with bicalutamide and anastrozole
The Journal of Pediatrics, 2006Co-Authors: Nerissa C Kreher, Ora H. Pescovitz, Paul Delameter, Anatoly Tiulpakov, Zeev HochbergAbstract:This report describes the use of bicalutamide and anastrozole in two subjects with familial male-limited Precocious Puberty. Clinical improvements include decreased facial acne and pubic hair. Most importantly, a marked decrease in growth velocity and skeletal advancement has been achieved.
