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.
Journal of pediatric endocrinology metabolism JPEM