Familial early puberty: presentation and inheritance pattern in 139 families.

Adélaïde Durand,Anu Bashamboo,Raja Brauner,Ken Mcelreavey

doi:10.1186/s12902-016-0130-x

Adélaïde Durand, Anu Bashamboo + Show 2 more

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https://doi.org/10.1186/s12902-016-0130-x

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Abstract

BackgroundThe mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. The coexistence in the same family of central precocious puberty and advanced puberty, both representing early puberty, suggests that they may represent a clinical spectrum of the same trait due to early activation of the GnRH pulse generator. We therefore evaluated the mode of inheritance of early puberty in a large series of familial cases.MethodsA retrospective, single center study was carried out on 154 probands (116 girls and 38 boys), from 139 families seen for idiopathic central precocious puberty (onset before 8 years in girls and 9–10 years in boys, n = 93) and/or advanced puberty (onset between 8 and 10 years in girls and 10 and 11 years in boys, n = 61) seen over a period of 8 years.ResultsOf the 139 families, 111 (80.4 %) had at least one affected 1st degree relatives, 17 (12 %) had only 2nd, 5 (3.6 %) only 3rd and 3 (2.2 %) had both 2nd and 3rd degree affected individuals. In the two remaining families, the unaffected mother had affected girls from two unaffected fathers. In the majority of families the inheritance of the phenotype was consistent with autosomal dominant mode of transmission with incomplete penetrance. An exclusively maternal mode of transmission could be observed or inferred in 83 families, paternal in only 2 families (p < 0.0001) and both maternal and paternal modes in 15 families.In the 139 families, 374 cases of early puberty were identified of whom 315 (84.2 %) were affected females and 59 (15.8 %) affected males (p < 0.0001). Twenty one percent of families had exclusively precocious puberty, 25 % had exclusively advanced puberty and 54 % had combinations of both.ConclusionsThe data confirm the high incidence of affected girls with familial early puberty. The mode of inheritance of the phenotype is predominantly maternal. More than half of the families included both precocious and advanced puberty suggesting similar genetic factors.

Highlights

The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition
Central precocious puberty (PP) was diagnosed by breast development before the age of 8 years accompanied by the presence of pubic or axillary hair, a growth rate greater than 2 standard deviation score (SDS) the year before clinical evaluation and/or a bone age (BA) more than 2 years above the chronological age [14]
The mean testicular volume was pubertal at the initial evaluation except in 3 PP boys and one boy with Advanced puberty (AP) who presented with pubic hair development followed by testicular enlargement before 9–10 years in PP or at 10–11 years in AP

Summary

Introduction

The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. The coexistence in the same family of central precocious puberty and advanced puberty, both representing early puberty, suggests that they may represent a clinical spectrum of the same trait due to early activation of the GnRH pulse generator. Central precocious puberty (PP) is defined as the development of sexual characteristics before the age of 8 years in girls and 9–10 years in boys and this is due to the premature activation of the hypothalamo-pituitary-gonadal axis [1]. Advanced puberty (AP) is defined as the onset of puberty in girls at 8–10 years and in boys at 10–11 years. Evidence to support a genetic cause of PP is suggested by familial clustering with up to 27.5 % of central PP cases are familial [7]. The percentage of familial cases may be higher because some patients defined as sporadic may have had family members with AP/PP in previous generations and patients with AP

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