Pattern of inheritance and analysis of clinical and cerebral MRI features of familial cases of central precocious puberty

Background: Many clinical observations show that central precocious puberty (CPP) may be in some cases familial. However, the scientific support to this assumption remains sparse up to now. Objective and hypotheses: The aim of the present study was to define a pattern of inheritance of familial CPP, and to identify possible clinical differences between familial (FPP) and sporadic (SPP) forms of CPP. Methods: We studied 110 patients affected by CPP (104 F, 6 M). The family tree of each patient was analysed and all information regarding the age of puberty and of menarche, and the presence of CPP among first and second degree relatives was collected. Results: Forty-one cases (37.3%; 40 F, 1M) met the criteria for FPP and the remaining 69 cases (62.7%; 64 F, 5 M) were SPP. The FPP showed a pattern of inheritance that was autosomal dominant in 24 (58.5%) cases, autosomal dominant with incomplete sex-dependent penetrance in 16 (39%) girls and autosomal recessive in only 1 (2.5%) case. The age at onset and the age at diagnosis of CPP did not differ between FPP and SPP, the girls with FPP showed a higher BMI-SDS than girls with SPP (2.77 ± 2.28 SD vs 1.72 ± 1.71SD; P=0.0402) and a greater bone age acceleration (2.12yrs ± 1.28 SD vs 1.56yrs ± 1.32 SD; P=0.0275). MRI showed CNS anomalies in 14/69 (20%) children with SPP and in 7/41 (17%) children with FPP. Conclusions: A familial origin was found in 1/3 of cases with CPP. Girls with FPP have a higher BMI and bone age maturation than those with SPP. CNS abnormalities were found either in SPP either in FPP and do not allow to exclude the need of performing cerebral MRI in FPP. The high prevalence of FPP suggests a careful inquiry regarding precocious puberty in young siblings and first-degree cousins of a child diagnosed with CPP