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J L Chaussain

Publications and source records attributed to J L Chaussain.

At least 73 records · Page 4Linked to original sources
PubMed1996

Gonadotropin-releasing hormone agonist treatment of girls with constitutional short stature and normal pubertal development.

GnRH agonists have been proposed to improve final height in patients with constitutional short stature. We treated 31 girls, aged 11.9 +/- 1 yr (mean +/- SD), with short stature, recent pubertal onset and predicted final height of 155 cm or less with depot triptorelin. During the 23 +/- 4 months of treatment, bone age progression was 0.6 +/- 0.3 bone age yr/yr, and growth velocity declined from 7 +/- 2 to 4 +/- 0.8 cm/yr (P < 0.0001). Height prognosis, calculated by the Bayley-Pinneau method, progressed from 149.6 +/- 3.4 to 151.8 +/- 4 cm at the end of treatment (+2.2 +/- 2.6 cm; P < 0.0001). When treatment was interrupted, growth velocity slightly increased to 4.6 +/- 1.6 cm/yr, and bone age maturation was accelerated: 1.3 +/- 0.4 bone age yr/yr during the first posttreatment year. At the last visit, 26 +/- 9 months after interruption of treatment, bone age was 14.9 +/- 1.3 yr (> or = 13.5 yr in all patients), height was 149.1 +/- 4 cm, and final height prognosis was 150.6 +/- 3.6 cm. Final height prognosis was 1 +/- 2.3 cm greater than pretreatment height prognosis (P < 0.02) and 1.2 +/- 2.2 cm below the height predicted at the end of the treatment (P < 0.01). No major side-effect was observed. Height SD score decreased during treatment with GnRH agonist from -2.3 +/- 0.9 to -2.7 +/- 0.7 SD score (P < 0.0001). We conclude that 2 yr of depot triptorelin-induced pubertal delay has a limited effect on near-final height in girls with constitutional short stature and that the growth benefit observed does not currently justify the use of GnRH agonists, given their cost and potential side-effects.

Adolescent↗
PubMed1996

Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France.

We diagnosed Cruetzfeldt-Jakob disease in 34 patients (16 definite, 18 probable) who had received human growth hormone extract for various period of time (mean +/- SD, 2.9 years), but particularly during the period between January 1984 and July 1985, a potential high-risk factor. Disease duration for deceased patients (n = 30) was 17 +/- 9 months. The clinical picture was homogeneous, starting with cerebellar ataxia and ocular motor disorders in about 90% of the patients. Neurologic deterioration, including dementia and myoclonic jerks, occurred within months. The high number of cases (1.5% of those treated between 1959 and 1988, 3% of those treated during the putative high-risk period) is still unexplained. We discuss the possibility that new cases will be detected,the risk of contaminating the general public, and the sanitary measures undertaken to prevent this.

Adolescent↗
PubMed1996

Testicular dysgenesis does not affect expression of anti-müllerian hormone by Sertoli cells in premeiotic seminiferous tubules.

Anti-Müllerian hormone (AMH) immunoreactivity was studied on paraffin sections obtained from archival testicular biopsies of 29 children with intersex disorders and of 22 controls. Strong AMH immunoreactivity was observed in Sertoli cell cytoplasm from 8 fetal weeks until puberty. During pubertal maturation, in both normal and intersex patients, AMH expression was present in premeiotic seminiferous tubules, but was no longer detected in neighboring tubules with meiotic development. AMH immunostaining was abolished in the testis of one patient with persistent Müllerian ducts due to a mutation of the AMH gene, but was conserved in the testes of two patients with mutations of the AMH receptor gene. Testicular dysgenesis usually results in sexual ambiguity, with low testosterone and AMH serum levels and persistence of Müllerian derivatives. AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma. In patients with asymmetric gonadal differentiation, the streak gonad was AMH-negative. In conclusion, secretion of AMH is a constitutive feature of the immature Sertoli cell and its expression is altered only by mutations of the AMH gene, but not by gonadal dysgenesis. The degree of regression of Müllerian ducts and serum AMH levels reflect the number, not the functional value, of Sertoli cells present in the immature testis.

Adolescent↗
PubMed1996

A novel mutation in the putative DNA helicase XH2 is responsible for male-to-female sex reversal associated with an atypical form of the ATR-X syndrome.

We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the alpha-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of alpha-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. We screened the XH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3' splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene.

Abnormalities, Multiple↗
PubMed1996

Growth hormone insensitivity syndrome (Laron syndrome): main characteristics and effects of IGF1 treatment.

Growth hormone (GH) insensitivity is a pathological state characterized by a disturbance of the physiological relationship between GH secretion, synthesis of insulin-like growth-factor I (IGF-1) and the biological actions of GH. Laron syndrome, the prototype for GH insensitivity, is most often due to GH receptor deficiency. However, this syndrome is heterogeneous in terms of growth characteristics, bio-chemical features and, most importantly, genetic defects. Recent data have indicated that partial GH receptor deficiency could be involved in children with apparently idiopathic short stature. Laron syndrome, because of extreme growth deficiency and a lack of alternative treatment, was the first clinical situation in which recombinant human IGF-1 was used. IGF-1 accelerates growth rate in most patients, induces subtle modifications of the craniofacies and decreases fat mass. However, it is still too early to evaluate the long-term effects of IGF-1 on final height. Tolerance to the drug has been excellent in all reported trials. The major (but rare) side effects are transient intracranial hypertension and hypokalemia. Generalization of data obtained in Laron syndrome to other clinical situations should take account of the profound alterations in IGF-1 pharmacokinetics resulting from a deficiency in IGF-binding proteins.

Genetic Heterogeneity↗
PubMed1996

Role of magnetic resonance imaging in the diagnosis and prognosis of growth hormone deficiency.

OBJECTIVE: In patients with congenital GH deficiency (GHD), magnetic resonance imaging (MRI) has revealed morphological abnormalities such as pituitary hypoplasia, absence of the stalk and ectopia of the posterior pituitary (PPE). Our study was aimed at investigating the possible relationship between neuroradiological images and the presence of isolated GH or multiple pituitary hormone deficiency. DESIGN: We studied 121 patients, aged 0.3-25 years, with isolated GHD (IGHD, 81 cases) or multiple pituitary hormone deficiency (MPHD, 40 cases). Of 81 IGHD patients, 50 were at prepubertal and 22 at pubertal age, while 9 had a delayed onset of puberty. Out of 40 MPHD patients, 25 were at prepubertal age and 15 at the age of puberty. RESULTS: Pituitary hypoplasia, defined as a gland with a height of less than -2 SD for age, was observed more frequently in prepubertal (66%) than pubertal (18%) IGHD patients. It was also found in the majority of MPHD patients of prepubertal (76%) and pubertal age (80%), and of IGHD patients with delayed onset of puberty (100%). Mean +/- SEM pituitary height was significantly lower (P < 0.001) in both prepubertal IGHD (-2.70 +/- 0.20 SD) and MPHD children (-3.10 +/- 0.39 SD) than in IGHD patients with normal onset of puberty (-1.55 +/- 0.2 SD). A significantly greater pituitary height was observed in IGHD patients with normal onset of puberty (-1.55 +/- 0.20 SD) than in MPHD patients at the age of puberty (-4.38 +/- 0.61 SD, P < 0.001) and in IGHD subjects with delayed onset of puberty (-4.06 +/- 0.41 SD, P < 0.001). An important increase (P < 0.02) in the height of the pituitary gland was found in 6 of the 9 patients with delayed puberty when they were re-evaluated after completing their spontaneous pubertal development. The frequency of other MRI abnormalities (PPE, stalk transection) was significantly higher in MPHD patients than in IGHD patients (P < 0.001). CONCLUSION: Our results confirm the usefulness of MRI in the evaluation of children affected by GH deficiency. The association of gland hypoplasia with other MR abnormalities could suggest the presence of multiple anterior pituitary deficiencies. Finally, puberty seems to play an important role in the increase of pituitary size in multiple pituitary hormone deficiency and isolated GH deficiency patients.

Adolescent↗
PubMed1995

Gonadal dysgenesis in del(18p) syndrome.

We report on a girl with syndromal gonadal dysgenesis and a de novo del(18p). Genetic factors controlling gonadal development are located not only on the X chromosome, but also on autosomes. The present case suggests that one of these genes is situated on 18p. We conclude that patients with del(18p) syndrome should be evaluated for gonadal dysgenesis.

Child, Preschool↗
PubMed1995

Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD.

We report the detection of a homozygous G to A mutation converting codon Gly15 into Asp15 in the type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) gene in a male pseudo-hermaphrodite born from consanguineous parents and suffering from severe salt-losing 3 beta-HSD deficiency. To investigate further the potential involvement of residue 15 in the beta alpha beta dinucleotide-binding fold, we have studied the effect of substituting Gly15 for Ala15. We assessed the effect of the G15D and G15A missense mutations on enzymatic activity by analyzing mutant enzymes generated by site-directed mutagenesis of type II 3 beta-HSD cDNA after their transient expression in COS-1 cells. In intact transfected cells, after a 2-h incubation, the percentage of conversion of [3H]pregnenolone (PREG) into [3H]progesterone (PROG) was 35% and 50% for the G15A and native type II 3 beta-HSD enzymes, respectively, whereas no detectable activity was observed in cells expressing the G15D protein. This finding is in agreement with the severity of the disease in the homozygote G15D index case. On the other hand, in homogenates from cells transfected with the normal pCMV-type II 3 beta-HSD plasmid or with the mutated pCMV-G15D or pCMV-G15A plasmid, the Km values for PREG were 0.72 microM, 3.2 microM, and 3.4 microM, respectively, when incubated for 1 h in the presence of excess (1 mM) NAD+. Moreover, the expressed G15D and G15A proteins had decreased affinities for NAD+ with Km values of 113 microM and 148 microM, respectively, compared with 22 microM for normal type II 3 beta-HSD.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Testicular degeneration in three patients with the persistent müllerian duct syndrome.

UNLABELLED: The persistent müllerian duct syndrome, characterized by the presence of uterus and tubes in males, is a familial disorder due to defects of synthesis or action of anti-müllerian hormone, a Sertoli cell glycoprotein responsible for the regression of müllerian derivatives in normal male fetuses. Patients are normally virilized and testicular production of testosterone is normal. Both testes may be cryptorchid; alternatively, one may be descended into the inguinal canal or scrotum, together with the müllerian derivatives, a condition known as "hernia uteri inguinalis". We have recently observed three patients affected by the persistent müllerian duct syndrome who experienced progressive degeneration of testicular tissue. In two, functional testicular tissue was still present some months after birth, but deteriorated progressively later. In one patient, testicular tissue was already absent at birth, but the normal virilization of external genitalia indicated that testicular degeneration must have occurred late during fetal life, after the expected time of regression of male müllerian ducts. CONCLUSION: The high incidence of degeneration of testicular tissue in the persistent müllerian duct syndrome could be indirectly linked to anatomical abnormalities which could favour testicular torsion, known to induce testicular regression.

Chronic Disease↗
PubMed1995

Final height after long-term growth hormone treatment in Turner syndrome. European Study Group.

OBJECTIVES: To study final height after long-term growth hormone (GH) treatment in girls with Turner syndrome (TS). PATIENTS: One hundred fifty three patients with TS, participating in five European trials, were included. They started GH treatment in 1987-1989 at an age of 10 years or older. Mean age at start of treatment ranged between 11.7 and 14.6 years among countries and mean bone age between 9.4 and 11.8 years. Fourteen girls were lost to follow-up, leaving 139 for analysis. Most girls have now attained final height (FH), defined as a linear growth velocity (GV) of 4 mm/yr or less, measured over at least 6 months (group 1, n = 56), or near-FH, defined as a GV of 5 to 9 mm/yr (group 2, n = 22). Sixty-one girls were still growing 10 mm/yr or more. METHODS AND MAIN RESULTS: At the last measurement, mean (SD) height was 150.7 (4.9) cm in group 1 and 148.5 (5.1) cm in group 2. The differences between FH and projected final height based on extrapolation of the initial height-standard deviation score on Turner syndrome reference values, were 2.9 (3.8) and 3.0 (3.3) cm, respectively. The mean gain over the Bayley-Pinneau prediction of FH was 3.3 (3.9) cm in both groups. No significant differences between countries were found. The range of gains over projected height (-4.7 to 12.1 cm) was large, and 25% of gains were 5 cm or more. Gain over initial projection was strongly related to initial growth delay and to growth response during the first 2 years of treatment. A logistic regression model is presented that predicts gain of more than 5 cm with a positive predictive value of 62% and a negative predictive value of 84%. CONCLUSIONS: Long-term GH treatment in girls with TS, starting treatment at a relatively advanced age ( > 10 years) resulted in a modest mean gain in FH of 3 cm, with wide interindividual variation.

Adolescent↗
PubMed1995

Characterization of heterogeneous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty.

Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. A heterozygous mutation encoding substitution of Asp578 with Gly in transmembrane helix 6 of the G protein-coupled receptor for luteinizing hormone (LHR) has been found in affected males from nine American FMPP families. Cells expressing the mutant LHR exhibit markedly increased cyclic adenosine monophosphate (cAMP) production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LHR. We have now analyzed genomic DNA from affected males from six additional FMPP families. PCR was used to amplify a fragment of the LHR gene encoding amino acid residues 441-594. None of the six new samples contained the Asp578-->Gly mutation, as indicated by absence of digestion with MspI. PCR products were then screened for heterozygous mutations using temperature-gradient gel electrophoresis. DNA fragments from two of the patients migrated abnormally. Direct sequencing of PCR product from one affected German male revealed a heterozygous mutation (ATG-->ATA) encoding Met571-->Ile at the cytoplasmic end of helix 6, the same mutation that has been reported in another European FMPP kindred. Affected males in the second family had a novel Thr577-->Ile mutation (ACC-->ATC). Mutations in different portions of the LHR or in a different gene may be responsible for disease in the other FMPP kindreds. Agonist binding and functional coupling of the mutant receptors to the cAMP and inositol phosphate pathways were studied by transiently expressing them in COS-7 cells. Agonist affinity was unaffected by the mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Final height in Turner syndrome patients treated with growth hormone.

The first treatment trials on patients presenting with Turner syndrome were successful in accelerating growth velocity. It is therefore essential to know the final height of the patients who were treated in order to ascertain whether or not growth hormone treatment increases final height. We are reporting on a group of 117 patients with Turner syndrome whose growth hormone treatment was initiated in 1986. The mean growth hormone dose was 0.74 IU/kg/week for an average period of 4 years. At the start of treatment, the patients' chronological age was 129/12 years, height -3.8 +/- 1.0 standard deviation scores (SDS) and bone age 10.5 +/- 2.1 years. Mean final height was 147.7 +/- 5.6 cm, i.e. a gain of 1.5 SDS. We noted no significant difference due to the type of chromosomal abnormality, nor to oxandrolone or estrogen-associated treatment. A significant correlation was found between final height, mean parental height, the duration of the treatment, height SDS at the start of treatment and growth hormone peak during pharmacological stimulation tests. However, there was no correlation between growth hormone dosage, chronological age and bone age at the start of treatment. These results show that the growth hormone treatment improves the final heights of patients with Turner syndrome.

Age Determination by Skeleton↗
PubMed1995

Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group.

We evaluated the pituitary and gonadal suppression in 40 girls and nine boys treated with depot leuprorelin (3.75 mg sc if body weight > or = 20 kg, 1.87 mg if body weight < 20 kg) every 28 days for central precocious puberty. Gonadal suppression was obtained in most of the children with this dose: 3 months after initiation of the treatment, 85% of children had a peak plasma luteinizing hormone response to gonadotropin-releasing hormone < 3 IU/l and the gonadal axis remained suppressed throughout the duration of the study (up to 24 months). Four patients required higher doses of leuprorelin to achieve suppression. In two girls, a cutaneous reaction to the drug was associated with incomplete suppression and the treatment had to be interrupted. Plasma leuprorelin levels tended to increase from day 3 to day 28 after injection. Residual leuprorelin levels measured 28 days after injection were stable during the first year of the study. We conclude that an initial dose of depot leuprorelin of 3.75 mg sc every 28 days is efficient in most children with central precocious puberty.

Bone Development↗
PubMed1994

Diagnosis of Cushing's disease in children: a challenge for the radiologist.

Cushing's disease is the most common cause of Cushing's syndrome in children and is almost always related to over secretion of ACTH by the pituitary gland. It is important to identify a secreting adenoma prior to surgery. Seven cases studied with MRI are reviewed. In five cases the MRI findings suggested adenoma. Three secreting adenomas were confirmed at surgery. One case was in fact a cyst of the pars intermedia, and nothing could be found in the last case. Two patients presented with apparently normal findings on MRI, which was confirmed. There is a close correlation between identifying an adenoma and the success of surgery.

Adenoma↗
PubMed1994

Molecular prenatal diagnosis of partial androgen insensitivity syndrome based on the Hind III polymorphism of the androgen receptor gene.

OBJECTIVE: Partial androgen insensitivity syndromes are the cause of genital ambiguity that is at times quite severe; there is, therefore, a high demand for prenatal diagnosis in families already afflicted with this syndrome. When the mutation has not been identified, the diagnosis can be made by the study of the polymorphisms of the androgen receptor gene. To perform molecular prenatal diagnosis in a family with partial androgen insensitivity syndrome, we studied the Hind III polymorphism of the androgen receptor gene on the trophoblastic DNA. The use of this restriction fragment length polymorphism tracked maternal X chromosome segregation and established prenatal diagnosis although the mutation had not yet been identified in this family. FAMILY: The mother had been previously described as heterozygous for the Hind III polymorphism and chromosomal segregation analysis showed that the affected allele was associated with the 6.7-kb Hind III fragment. MEASUREMENTS: Hind III RFLP with an androgen receptor gene cDNA probe was realized on the trophoblastic DNA, along with measurement of androgen binding activity on the trophoblastic cells. RESULTS: We detected the presence of the 6.7-kb fragment in the DNA of the trophoblastic cells suggesting the fetus was affected. Partial androgen insensitivity syndrome was confirmed by a considerable decrease in androgen binding activity on the trophoblastic cells and by sonography of the fetus. After a therapeutic abortion requested by the parents, the diagnosis was confirmed by clinical examination of the fetus, biochemical analyses of the fetal androgen receptor, and molecular studies of the fetal DNA. CONCLUSIONS: When the mutation of the androgen receptor gene has not been identified, Hind III polymorphism of the trophoblastic DNA is useful in the prenatal diagnosis of androgen insensitivity syndrome in high-risk families.

Androgens↗
PubMed1994

Adult height in children with prepubertal short stature secondary to intrauterine growth retardation.

In a retrospective study of 47 children seen before puberty for growth retardation secondary to intrauterine growth retardation (IUGR), 23 boys had a final height of 161.9 +/- 8.0 cm and 24 girls a final height of 147.6 +/- 7.2 cm, values that were significantly lower than the target heights of these patients (p < 0.001). This reduction in adult height indicates the possible usefulness of growth hormone therapy in children with IUGR.

Adolescent↗
PubMed1994

Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation.

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased (p < 0.0005) in groups B and C, with a greater increase in group C than in group B (p < 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.

Body Height↗