Guy Van Vliet

Centre jeunesse de Montréal-Institut universitaire, Montréal, Quebec, Canada

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Publications (170)779.91 Total impact

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    ABSTRACT: BackgroundDAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated.Methods We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional Sanger sequencing to search for causal genes. Lym1 mice were propagated and examined for endocrine developmental anomalies.ResultsMutations in the NFKB2 gene were identified in three of our families through whole exome sequencing, and in a fourth by direct Sanger sequencing. De novo origin of the mutations could be demonstrated in three of the families. All mutations lie near the C-terminus of the protein-coding region, near signals required for processing of NF¿B2 protein by the alternative pathway. Two of the probands had anatomical pituitary anomalies, and one had growth and thyroid hormone as well as ACTH deficiency; these findings have not been previously reported. Two children of one of the probands carried the mutation and have to date exhibited only an immune phenotype. No mutations were found near the C-terminus of NFKB2 in the remaining two probands; whole exome sequencing has been performed for one of these. Lym1 mice, carrying a similar Nfkb2 C-terminal mutation, showed normal pituitary anatomy and expression of proopiomelanocortin (POMC).Conclusions We confirm previous findings that mutations near the C-terminus of NFKB2 cause combined endocrine and immunodeficiencies. De novo status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed NFKB2 super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in Lym1 mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function.
    BMC Medical Genetics 12/2014; 15(1):139. · 2.54 Impact Factor
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    ABSTRACT: Background/Aims: Congenital primary hypothyroidism (CH) is a rare pediatric disorder estimated to occur in about 1:2,500 live births. Approximately half of these cases entail ectopic thyroid tissue, which is believed to result from a migration defect during embryogenesis. Approximately 3% of CH cases are explained by mutation(s) in known genes, most of which are transcription factors implicated in the embryology of the thyroid gland. Surprisingly, monozygotic (MZ) twins are usually discordant for CH due to thyroid dysgenesis, suggesting that most cases are not caused by transmitted genetic variation. One possible explanation is somatic mutation in genes involved in thyroid migration occurring after zygotic twinning. Such mutations should be observed only in the affected twin. Methods: To test the hypothesis of somatic mutation, we performed whole exome sequencing of DNA from three pairs of MZ twins discordant for CH with ectopic glands. Results: We found no somatic mutations exclusive to any of the three affected twins or in any of the unaffected twins. Conclusion: Either somatic mutations are not significant for the etiology of CH or else such mutations lie outside regions of the genome accessible by exome sequencing technology. © 2014 S. Karger AG, Basel.
    Hormone Research in Paediatrics 09/2014; · 1.55 Impact Factor
  • Johnny Deladoëy, Guy Van Vliet
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    ABSTRACT: Screening increases prevalence estimates for most diseases and congenital hypothyroidism (CH) is no exception, affecting one in 6700 children by clinical ascertainment and one in 3500 in the first surveys of systematic biochemical screening of newborns. Importantly, screening has resulted in the disappearance of intellectual disability due to CH. A further doubling in prevalence estimates has recently been reported, mostly accounted for by changes in screening algorithms; accordingly, the prevalence of overt CH has remained stable. Population-based registries that distinguish confirmed diagnoses from positive screening results have proved invaluable. These registries should include: etiology of CH based on imaging, ideally technetium scintigraphy; ethnicity; socio-educational data; input from the screening laboratories and pediatric endocrinologists. Efforts should now be directed at increasing the proportion of the world’s newborns screened for overt CH (currently 30%) and at determining if neonates with mild hyperthyrotropinemia also benefit from early treatment.
    Expert Review of Endocrinology &amp Metabolism 05/2014;
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    ABSTRACT: Background: Discordance of monozygotic twins for thyroid dysgenesis suggests that epigenetic mechanisms may underlie defects in thyroid gland development. This prompted us to evaluate whether differentially methylated regions (DMR) can be found between human thyroids (either eutopic or ectopic) and matched leukocytes. Methods: To compare the genome-wide methylation profile of thyroids and leukocytes, immunoprecipated methylated DNA was interrogated on human promoter plus CpG island tiling arrays. In addition, the methylation profile of the human FOXE1, PAX8 and NKX2.1 promoter was examined using bisulfite sequencing. Finally, the functional impact of CpG methylation of the promoter on FOXE1 expression was assessed with luciferase assays. Results: Genome-wide methylation profiling and bisulfite sequencing of CpG islands of PAX8 and NKX2.1 promoters revealed no DMR between thyroid and leukocytes. However, bisulfite sequencing revealed that the methylation level of two consecutive CpG dinucleotides (CpG14 and CpG15, which were not covered by the genome-wide array) in one CpG island of the FOXE1 promoter (-1600 to -1140 from the transcription start site) is significantly higher in leukocytes than in eutopic or ectopic thyroid tissues, suggesting that methylation of this region may decrease FOXE1 gene expression. Indeed, luciferase activities were decreased when FOXE1 promoter constructs were methylated in vitro. Moreover, derepression of luciferase activity was observed when methylation of CpG14 and CpG15 was prevented by mutations. Conclusion: We report a tissue-dependent DMR in the FOXE1 promoter. This DMR contains two consecutive CpG dinucleotides which are epigenetic modifiers of FOXE1 expression in non-tumoral tissues.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; · 6.31 Impact Factor
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    ABSTRACT: In adults, autonomous adenomas of the thyroid causing hyperthyroidism are relatively common and are most often due to somatic mutations that increase the constitutive activity of the thyroid-stimulating hormone receptor (TSHR). By contrast, autonomous adenomas in hyperthyroid children are exceptional and reports of their clinical and molecular characteristics are few. We reviewed papers describing 16 autonomous adenomas due to a somatic mutation activating the TSHR and diagnosed in patients younger than 18 years, to which we added two of our own unpublished observations in a 4- and 8-year-old with the same TSHR mutation (c.CAG>CAC; p.Asp633His). This revealed that (a) autonomous adenomas occur more often in the right lobe (11 of 14 with available information) and the associated hyperthyroidism tends to be more severe, possibly reflecting the richer vascular supply of the right thyroid lobe, and (b) mutations found in benign adenomas in children have been associated with cancer in adults, suggesting that malignancy requires a second 'hit' at a later age. © 2014 S. Karger AG, Basel.
    Hormone Research in Paediatrics 01/2014; · 1.55 Impact Factor
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    ABSTRACT: Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case. Although not fully comprehensive, it aims at providing relevant clinical knowledge on thyroid diseases of the neonate, the child, and the adolescent. © 2014 S. Karger AG, Basel.
    Endocrine development 01/2014; 26:214-44.
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    ABSTRACT: Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy. © 2014 S. Karger AG, Basel and The Endocrine Society.
    Hormone Research in Paediatrics 01/2014; 81(2):80-103. · 1.55 Impact Factor
  • Guy Van Vliet, Johnny Deladoëy
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    ABSTRACT: Screening for a disease begins a process that should lead to confirmation of the diagnosis, establishment of the etiology, optimal treatment and documentation of outcome. In newborns referred for an elevated thyroid-stimulating hormone (TSH) level on the screening specimen, a detailed family and personal history should be obtained, and a careful clinical examination should be performed. Hypothyroidism should be confirmed by measuring serum TSH and thyroxine (T4) and the underlying etiology established by sodium pertechnetate scintigraphy. Treatment should be started promptly with an adequate dose of levothyroxine. Clinical and biochemical monitoring should be frequent during the first 3 years of life, when the brain can suffer irreversible damage from hypothyroidism. Except in patients with thyroid ectopy or with true athyreosis, permanence of hypothyroidism should be confirmed after 3 years of age by withholding treatment for at least 4 weeks and measuring serum TSH and T4 off therapy. Growth, psychomotor development and school progression should be documented, especially in children from socially disadvantaged families. Transition to adult care is particularly important for females, who should receive counseling about increased levothyroxine needs during future pregnancies. Cognitive outcome has improved dramatically with screening for overt congenital hypothyroidism, but the benefits from treatment of mild isolated hyperthyrotropinemia remain unproven. © 2014 S. Karger AG, Basel.
    Endocrine development 01/2014; 26:50-9.
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    ABSTRACT: In 2001, a chart review of children referred to the authors' endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors' service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners. Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies. Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%). The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors' specialty clinic while promoting medical education.
    Paediatrics & child health 12/2013; 18(10):533-7. · 1.03 Impact Factor
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    ABSTRACT: Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. All the reported cases occurred sporadically. Although several causal genes of HPE and ectrodactyly have been identified, the genetic cause of Hartsfield syndrome remains unknown. We hypothesised that a single key developmental gene may underlie the co-occurrence of HPE and ectrodactyly. We used whole exome sequencing in four isolated cases including one case-parents trio, and direct Sanger sequencing of three additional cases, to investigate the causative variants in Hartsfield syndrome. We identified a novel FGFR1 mutation in six out of seven patients. Affected residues are highly conserved and are located in the extracellular binding domain of the receptor (two homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Strikingly, among the six novel mutations, three are located in close proximity to the ATP's phosphates or the coordinating magnesium, with one position required for kinase activity, and three are adjacent to known mutations involved in Kallmann syndrome plus other developmental anomalies. Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome, consistent with the known roles of FGFR1 in vertebrate ontogeny and conditional Fgfr1-deficient mice. Our study shows that, in humans, lack of accurate FGFR1 activation can disrupt both brain and hand/foot midline development, and that FGFR1 loss-of-function mutations are responsible for a wider spectrum of clinical anomalies than previously thought, ranging in severity from seemingly isolated hypogonadotropic hypogonadism, through Kallmann syndrome with or without additional features, to Hartsfield syndrome at its most severe end.
    Journal of Medical Genetics 06/2013; · 5.70 Impact Factor
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    ABSTRACT: Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.
    The American Journal of Human Genetics 05/2013; 92(5):725-43. · 11.20 Impact Factor
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    ABSTRACT: OBJECTIVES: To describe the response of thyroid-stimulating hormone (TSH) to thyroid-releasing hormone in children and adolescents with Prader-Willi syndrome (PWS), and to compare TSH and total thyroxine (TT4) concentrations measured on neonatal screening for congenital hypothyroidism in children with PWS and controls. STUDY DESIGN: All participants had genetically confirmed PWS. The TSH responses to thyroid-releasing hormone, free thyroxine (fT4), and free triiodothyronine (fT3) were measured in 21 subjects (14 females and 7 males; mean age, 6.4 years). Capillary TT4 was measured on neonatal screening samples from 23 subjects with PWS (14 females and 9 males), each of whom was matched for birth weight and sex with 4 anonymized controls. RESULTS: One subject with PWS had tertiary hypothyroidism. TSH level increased from 1.37 mU/L at baseline to 39.6 mU/L at 20 minutes, 47.2 mU/L at 40 minutes, 44.5 mU/L at 60 minutes, and 47.2 mU/L at 120 minutes. fT4 concentration was 6.3 pmol/L, and fT3 concentration was 4.6 pmol/L. In the other 20 subjects, mean TSH level was 1.9 mU/L (range, 0.8-4.2 mU/L) at baseline and 21.8 mU/L (range, 10.0-46.7 mU/L) at 20 minutes (peak). Mean fT4 concentration (10.4 pmol/L; range, 8.2-13.5 pmol/L) was in the lower one-third of the normal range in 18 subjects, and mean fT3 concentration (6.1 pmol/L; range, 4.8-8.4 pmol/L) was above the median in 13 subjects. In neonates, mean TSH level was 3.1 mU/L (range, 0.4-10.0 mU/L) in subjects with PWS versus 3.3 mU/L (range, 0.0-7.0 mU/L) in controls, and mean TT4 in subjects with PWS was 111% (range, 17%-203%) that of controls (P = not significant). CONCLUSION: Thyroid function was normal in our newborn subjects. In older children, frank hypothyroidism was found in only 1 of our 21 subjects. Thus, levothyroxine treatment should not be routinely prescribed to youth with PWS.
    The Journal of pediatrics 04/2013; · 4.02 Impact Factor
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    ABSTRACT: Mutations in the NNT gene (nicotinamide nucleotide transhydrogenase), which is involved in NADPH generation in mitochondria, have recently been described in familial glucocorticoid deficiency. We report two patients, one with isolated glucocorticoid deficiency and the other with a combined glucocorticoid and mineralocorticoid deficiency. Through whole exome sequencing, both cases were found to carry two different NNT mutations, confirming previous results for these patients. Each patient also carries multiple heterozygous protein-altering mutations in other genes involved in steroid hormone biogenesis and regulation. The patient with a combined glucocorticoid and mineralocorticoid deficiency is a compound heterozygote for common missense variants in the ME3 gene (mitochondrial malic enzyme 3), the product of which also generates NADPH in mitochondria. Mutations in NNT are the likely proximal cause of the glucocorticoid deficiency in both patients, but genetic background effects may be important in modulating the specific phenotype of adrenal insufficiency.
    Journal of Genomes and Exomes. 03/2013; 2:19-30.
  • Johnny Deladoëy, Guy Van Vliet
    Nature Reviews Endocrinology 03/2013; · 11.03 Impact Factor
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    ABSTRACT: OBJECTIVES: To determine which biological or clinical variables may predict cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation following supraphysiological doses of glucocorticoids in children. STUDY DESIGN: This retrospective study included all patients who underwent ACTH testing (1 μg) between October 2008 and June 2010 at the Sainte-Justine University Hospital Center, Montreal, after supraphysiological doses of glucocorticoids. RESULTS: Data from 103 patients (median age, 8.0 years; range, 0.6-18.5 years; 57 girls) were analyzed, revealing growth deceleration in 37% and excessive weight gain in 33%. Reasons for glucocorticoid treatment included asthma (n = 30) and hematologic (n = 22), dermatologic (n = 19), rheumatologic (n = 16), and miscellaneous (n = 16) disorders. The following information was recorded: duration of glucocorticoid treatment (median, 374 days; range, 5-4226 days); duration of physiological hydrocortisone replacement (median, 118 days; range, 0-1089 days); maximum daily (median, 200 mg/m(2)/day; range, 12-3750 mg/m(2)/day) and cumulative (median, 16 728 mg/m(2); range, 82-178 209 mg/m(2)) doses, in hydrocortisone equivalents; and interval since the last dose (median, 43 days; range, 1-1584 days). Sixty-two patients (58%) exhibited a normal response (ie, peak cortisol >500 nmol/L) to ACTH stimulation. Peak cortisol level was not related to sex, prior morning cortisol level, duration of treatment, or cumulative glucocorticoid dose; 28% of the patients with normal baseline cortisol levels nevertheless demonstrated a subnormal response to ACTH. CONCLUSION: Given the absence of clinical or biological predictors of the cortisol response to ACTH after suppressive doses of glucocorticoids, physicians have only 2 options: (1) empirically advocate glucocorticoid stress coverage during 18 months after cessation of high-dose glucocorticoid treatment; or (2) perform serial ACTH testing in all such patients until a normal peak cortisol level is attained.
    The Journal of pediatrics 02/2013; · 4.02 Impact Factor
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    ABSTRACT: A 15-year-old girl presented with chorea as a first sign of Graves' hyperthyroidism. Chorea abated with antithyroid drug treatment and reappeared when hyperthyroidism recurred but not when thyrotropin receptor antibodies increased after administration of (131)I. Therefore, chorea in this patient is associated with hyperthyroxinemia and not with autoantibodies.
    PEDIATRICS 01/2013; · 4.47 Impact Factor
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    ABSTRACT: Context:A 4-year-old girl and a 4-month-old boy presented with hypoglycemia, normal electrolytes, low cortisol, and high ACTH. A diagnosis of primary adrenal insufficiency was made and initial treatment was with glucocorticoids and mineralocorticoids. The genes known to cause ACTH resistance were normal. Whole exome sequencing revealed that the girl was compound heterozygous for POMC mutations: one previously described null allele and one novel p.R8C mutation in the sequence encoding ACTH and α-MSH. The boy was homozygous for the p.R8C mutation.Hypothesis:The p.R8C ACTH mutant is immunoreactive, but the mutant peptides, ACTH-R8C and α-MSH-R8C, are bioinactive.Methods:Methods included whole exome sequencing, Sanger sequencing, peptide synthesis, ACTH immunoradiometric assay, hormone binding, and activation assays in cells expressing melanocortin receptors.Results:ACTH-R8C was immunoreactive but failed to bind and activate cAMP production in melanocortin-2 receptor (MC2R)-expressing cells, and α-MSH-R8C failed to bind and stimulate cAMP production in MC1R- and MC4R-expressing cells.Conclusion:These are the first documented cases of glucocorticoid deficiency due to the secretion of an ACTH molecule that lacks biological bioactivity but conserves immunoreactivity. POMC mutations should thus be considered in patients presenting with apparent ACTH resistance. Our findings also highlight a limitation to immunoassay-based diagnostics and demonstrate the value of genetic analysis. Establishing the molecular etiology of the disorder in our patients allowed cessation of the unnecessary mineralocorticoids. Finally, discovery of this mutation indicates that in humans, the amino acid sequence His(6)Phe(7)Arg(8)Trp(9) is important not only for cAMP activation but also for ACTH binding to MC2R.
    The Journal of Clinical Endocrinology and Metabolism 01/2013; · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVE: To analyze the clinical, hormonal, anatomical, and molecular characteristics of Leydig cell tumors, a very rare cause of progressive hyperandrogenism in children. STUDY DESIGN: Description of a 9-year-old boy with isosexual precocious pseudopuberty, and of a 12-year-old girl with rapidly progressive virilization, both due to a pure Leydig cell tumor. Review of all cases of pediatric Leydig cell tumors published since 1999 (when the first somatic mutations of the luteinizing hormone receptor were described) and reporting hormonal and/or molecular data. RESULTS: Boys (n = 24) are younger than girls (n = 12) at diagnosis (median 6.5 vs 13.0 years, P = .04). Plasma gonadotrophins are more often completely suppressed in boys (6 cases) than in girls (2 cases). Pure Leydig cell tumors are exceedingly rare in girls (2 cases), who most often have Sertoli-Leydig tumors. These tumors affect either testis equally (11 left, 13 right) but occur more often in the left ovary (8 left, 3 right). Activating mutations of the alpha-subunit of the G(s) stimulatory protein have not been found in either boys or girls and activating mutations of the luteinizing hormone receptor have only been found in boys. CONCLUSIONS: Leydig cell tumors in children display clinical, hormonal, anatomical, and molecular sexual dimorphism.
    The Journal of pediatrics 06/2012; · 4.02 Impact Factor
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    ABSTRACT: Thyroid ectopy results from the failure of the thyroid precursor cells to migrate from the primordial pharynx to the anterior part of the neck. Most ectopic thyroids are revealed by congenital hypothyroidism and present as a single round mass at the base of the tongue, with no other thyroid tissue. However, some cases have dual ectopy, with part of the tissue having partially migrated. We hypothesized that this occurs more frequently than previously reported. To determine the prevalence of dual ectopy, we reviewed the pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from thyroid ectopy diagnosed between 2002 and 2011 at our institution. We report a series of seven cases (9%) of dual ectopy, representing an incidence ranging from 1:50,000 to 1:70,000. Almost one in 10 cases with congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests that two populations of cells diverged at an early stage of development, which may arise from insufficient signaling gradients in surrounding tissues during early organogenesis or may indirectly support the polyclonal nature of the thyroid.
    The Journal of Clinical Endocrinology and Metabolism 03/2012; 97(6):E978-81. · 6.31 Impact Factor

Publication Stats

3k Citations
779.91 Total Impact Points

Institutions

  • 2014
    • Centre jeunesse de Montréal-Institut universitaire
      Montréal, Quebec, Canada
  • 1995–2013
    • Université de Montréal
      • Department of Pediatrics
      Montréal, Quebec, Canada
  • 2011
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
    • University of Geneva
      • Division of Paediatrics
      Genève, GE, Switzerland
  • 2007–2011
    • Centers for Disease Control and Prevention
      • National Center on Birth Defects and Developmental Disabilities
      Druid Hills, GA, United States
  • 1999–2011
    • University of Manitoba
      • Department of Pediatrics and Child Health
      Winnipeg, Manitoba, Canada
    • Laval University
      Québec, Quebec, Canada
    • McGill University
      • Department of Pediatrics
      Montréal, Quebec, Canada
  • 1995–2011
    • CHU Sainte-Justine
      Montréal, Quebec, Canada
  • 2010
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2008–2009
    • Massachusetts General Hospital
      • Reproductive Endocrine Unit
      Boston, MA, United States
  • 1980–2008
    • Vrije Universiteit Brussel
      • Department of Pediatrics
      Bruxelles, Brussels Capital Region, Belgium
  • 1992–2006
    • Université du Québec à Montréal
      Montréal, Quebec, Canada
  • 1988–1998
    • Hôpital Universitaire des Enfants Reine Fabiola
      Bruxelles, Brussels Capital Region, Belgium
  • 1991
    • KU Leuven
      • Department of Human Genetics
      Leuven, VLG, Belgium
  • 1987–1991
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
  • 1987–1990
    • Centre Hospitalier Universitaire Saint-Pierre
      Bruxelles, Brussels Capital Region, Belgium