title: Central precocious puberty in a boy with 22q13 deletion syndrome and NOTCH-1 gene duplication.
abstract: The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis.
authors.forename: Aris
authors.initials: A
authors.lastname: Giannakopoulos
authors.forename: Helen
authors.initials: H
authors.lastname: Fryssira
authors.forename: Maria
authors.initials: M
authors.lastname: Tzetis
authors.forename: Athina
authors.initials: A
authors.lastname: Xaidara
authors.forename: Christina
authors.initials: C
authors.lastname: Kanaka-Gantenbein
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D020732:Cytogenetic Analysis; D057210:Delayed Diagnosis; D016903:Drug Monitoring; D020440:Gene Duplication; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006115:Greece; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011629:Puberty, Precocious / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics*; D012102:Reproductive Control Agents / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D012102:Reproductive Control Agents; D007987:Gonadotropin-Releasing Hormone