Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 ... Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The timing of puberty is associated with risks of subsequent disease: earlier age of menarche in girls is associated with increased risk of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Central precocious puberty has also been associated with an increased incidence of conduct and behavior disorders during adolescence (summary by Abreu et al., 2013). For discussion of genetic heterogeneity of central precocious puberty, see CPPB1 (176400).
Abreu et al. (2013) studied 15 patients, 8 female and 7 male, from 5 families with central precocious puberty associated with mutation in the MKRN3 gene (see MOLECULAR GENETICS). Each of the patients had clinical and hormonal features ... Abreu et al. (2013) studied 15 patients, 8 female and 7 male, from 5 families with central precocious puberty associated with mutation in the MKRN3 gene (see MOLECULAR GENETICS). Each of the patients had clinical and hormonal features typical of premature activation of the reproductive axis, including early pubertal signs such as breast development or testicular enlargement, pubic hair, advanced linear growth and bone age, and elevated basal luteinizing hormone (LH; see 152780) levels, elevated GnRH (152760)-stimulated LH levels, or both. The median age at onset of puberty in the girls was 5.75 years, ranging from 5.0 to 6.5 years, whereas in the boys it was 8.1 years, ranging from 5.9 to 8.5 years. All patients had normal MRI of the central nervous system.
Abreu et al. (2013) performed whole-exome sequencing in 40 members of 15 families with central precocious puberty and identified heterozygosity for 3 frameshift mutations and 1 missense mutation in the MKRN3 gene (603856.0001-603856.0004) in affected individuals from 5 ... Abreu et al. (2013) performed whole-exome sequencing in 40 members of 15 families with central precocious puberty and identified heterozygosity for 3 frameshift mutations and 1 missense mutation in the MKRN3 gene (603856.0001-603856.0004) in affected individuals from 5 of the families. Sanger sequencing confirmed the mutations, and there was complete cosegregation with the phenotype in each of the families. All affected family members inherited their mutations from their fathers, consistent with a paternally expressed imprinted gene; the 1 heterozygous carrier known to have inherited his mutation from his mother was unaffected.