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). - Genetic Heterogeneity of Central Precocious Puberty Central precocious puberty-2 (CPPB2; 615346) is caused by mutation in the MKRN3 gene (603856) on chromosome 15q11.
So-called isosexual precocious puberty is usually defined as onset of menarche in the female before age 8.5 years or pubertal changes in the male before age 10 years. Puberty may occur before 3 years of age. Adult height ... So-called isosexual precocious puberty is usually defined as onset of menarche in the female before age 8.5 years or pubertal changes in the male before age 10 years. Puberty may occur before 3 years of age. Adult height is reduced. These cases are often misdiagnosed as adrenogenital syndrome. Male-to-male transmission has been observed. Central precocious puberty refers to a gonadotropin-dependent type which results from premature activation of the hypothalamic-pituitary-gonadal axis (Teles et al., 2008). Rush et al. (1937) and Jacobsen and Macklin (1952) reported a family in which 27 males (but no females) in 4 generations showed sexual precocity. Hampson and Money (1955) suggested that female sexual precocity may be transmitted through the male. Jungck et al. (1957) observed transmission of male precocity through females. Ferrier et al. (1961) and Beas et al. (1962) reported families with affected brother and sister. Wilkins (1965) stated that 'among girls we also have seen a familial tendency to sexual precocity and have had one family in which both sexes were affected.' Precocious puberty is a more frequent occurrence in females than in males, but familial occurrence seems rarer in females. X-linked recessive inheritance was postulated by Vasquez et al. (1978), who observed 2 male cousins. Commenting on the rarity of familial precocious puberty in girls, Rangasami and Grant (1992) reported its occurrence in sisters at which puberty began with breast development at the age of 4 years and 5 years and three months, respectively. There appeared to be a premature activation of the hypothalamic-pituitary-gonadal axis as shown by increased secretion of LH and FSH. Prasher (1993) pointed out that hypothyroidism is occasionally accompanied by precocious puberty rather than delay of sexual maturation and that thyroid function should be checked in patients such as those reported by Rangasami and Grant (1992). Kalantaridou and Chrousos (2002) reviewed monogenic disorders of puberty. De Vries et al. (2004) investigated the mode of inheritance of familial precocious puberty and sought to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to their center for suspected precocious puberty, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy; 27.5%). The familial group was characterized by a significantly lower age of maternal menarche than the sporadic group (mean, 11.47 +/- 1.96 vs 12.66 +/- 1.18 years, P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs 78.1%, P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young sibs) assuming incomplete penetrance and 0.58 (0.65 after exclusion of young sibs) assuming complete ascertainment. The authors concluded that these results suggest autosomal dominant transmission with incomplete, sex-dependent penetrance. Teles et al. (2008) described an 8-year-old girl referred for evaluation of precocious puberty. Premature breast development with slow progression had been observed since birth. At 7 years of age breast growth accelerated and pubic hair was noted. Additional pubertal signs such as acne, oily skin, axillary hair, and menstrual bleeding were absent. There were no cafe au lait spots. At 8 years of age height was 131.5 cm and weight was 26.7 kg, with a bone age of 11 years; breast development was Tanner stage 4, and pubic hair Tanner stage 2. Treatment with an analog of gonadotropin-releasing hormone receptor (GNRHR; 138850) was initiated and maintained for 4 years. The diagnosis of central precocious puberty was confirmed by a satisfactory response to the treatment, including partial regression of breast development, decrease in growth velocity, arrest of bone maturation, reduction of ovarian size, and gonadotropin suppression along with the returned prepubertal estradiol levels. Spontaneous menarche occurred at age 12 and was followed by regular menses. The patient's adult height was 152.2 cm.
Teles et al. (2008) demonstrated that a heterozygous activating mutation in the GPR54 gene (604161.0006) can cause central precocious puberty. The patient had had thelarche from birth, but with slow progression, suggesting an early, persistent, and mild increase ... Teles et al. (2008) demonstrated that a heterozygous activating mutation in the GPR54 gene (604161.0006) can cause central precocious puberty. The patient had had thelarche from birth, but with slow progression, suggesting an early, persistent, and mild increase in estrogen secretion. Isolated thelarche was ruled out on the basis of progressive secondary sexual development and accelerated growth and skeletal maturation.