Central Precocious Puberty and Response to GnRHa Therapy in Children with Cerebral Palsy and Moderate to Severe Motor Impairment: Data from a Longitudinal, Case-Control, Multicentre, Italian Study

Abstract

Background Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, p = 0.023). Conclusions Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients.

High prevalence of syndromic disorders in patients with non-isolated central precocious puberty

“…The prevalence of CPP in children with cerebral palsy and moderate or severe motor impairment is unknown, as the available data are limited (15,33,34). A higher prevalence of variable degrees of early sexual maturation was reported in 161 girls with neonatal encephalopathy As expected, our patients also frequently displayed other types of alteration to brain structure (data not shown).…”

“…It has been suggested that severe brain damage and antiepileptic drugs probably affect neurotransmitter pathways involved in gonadotropin control and that the normal hypothalamic inhibition of gonadotropins may be lost (34). Limited data have also been reported for patients with RASopathies and CPP, such as our patients with cardio facio cutaneous syndrome (BRAF mutation) (19, 36) or epidermal nevus syndrome with HRAS gene mutation (37,38,39).…”

Disorders of Puberty in Severely Neurologically Impaired Children: Is Delayed Puberty an Underestimated Problem?

“…NI children could experience disorders of puberty in term of precocious or delayed puberty. Pediatric patients affected by neurodevelopmental disabilities are 20 times more at risk of premature pubertal changes compared to the general population (4). Many insults to the central nervous system including birth asphyxia, congenital malformation and infections can cause PP (4).…”

“…Pediatric patients affected by neurodevelopmental disabilities are 20 times more at risk of premature pubertal changes compared to the general population (4). Many insults to the central nervous system including birth asphyxia, congenital malformation and infections can cause PP (4). Severe brain damage and use of antiepileptic medication may affect a number of neurotransmitter pathways involved in gonadotropin control, inducing an activation of the hypothalamic-pituitary-gonadal axis (13).…”

“…In children and adolescents with disabilities, the pattern of sexual maturation may differ from that of children in the general population (3) with possible abnormal puberty development. Brain injury during structural and functional brain maturation in the pre-, peri-, or post-natal period may negatively impact the development of pubertal changes (4).…”