Central precocious puberty after resection of a virilising adrenocortical oncocytic tumour.

Adrenocortical oncocytic tumours are a histological subtype of adrenal neoplasms with a distinctive morphological appearance. Since these tumours are composed of cells of the adrenal cortex, they may act as functional tumours with excess hormone production. They may cause Cushing's syndrome, inappropriate virilisation or precocious puberty. Though rare during childhood, adrenocortical oncocytic tumours should be suspected in a child with peripheral precocious puberty and marked elevation of dehydroepiandrosterone sulfate levels. We describe a 6-year girl who presented with peripheral precocious puberty due to a functional adrenocortical oncocytic tumour. Three months after tumour removal, she developed true central precocious puberty. This report highlights that peripheral precocious puberty may trigger central precocious puberty, particularly after resolution of the underlying cause of the peripheral precocious puberty.

The effect of growth hormone treatment in a child with tricho-rhino-phalangeal syndrome: A case report and review of the literature.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal malformations including short stature, cone-shaped phalangeal epiphyses and Perthes-like changes of the hip. We describe the response to growth hormone (GH) treatment in a boy with TRPS. The patient presented at age 3.5 years for evaluation of short stature (-3.2SD). On physical examination, the characteristic facial phenotype of TRPS was noted. Radiographs showed cone-shaped phalangeal epiphyses and bilateral small and fragmented femoral heads. The diagnosis was confirmed by Sanger sequencing of the TRPS1 gene. Two GH stimulation tests revealed GH deficiency, and GH treatment was initiated. Subsequently, growth velocity improved, as did the radiographic appearance of the femoral epiphyses, as seen on sequential pelvis radiographs. This observation suggests the possibility of a beneficial effect of GH treatment on both height and epiphyses status in TRPS patient with GH deficiency. Further studies are needed to support the observation.

Neonatal osteoma cutis due to a mutation in GNAS.

We describe a 4-week-old baby boy who presented with white firm cutaneous nodules and failure to thrive. He did not have dysmorphic features, and laboratory tests including serum calcium, phosphorous, thyroid function, and parathyroid hormone level were within normal ranges. Whole exome sequencing revealed an inactivating mutation in GNAS that was previously described as causing pseudohypoparathyroidism.

PLS3 Deletions Lead to Severe Spinal Osteoporosis and Disturbed Bone Matrix Mineralization.

Mutations in the PLS3 gene, encoding Plastin 3, were described in 2013 as a cause for X-linked primary bone fragility in children. The specific role of PLS3 in bone metabolism remains inadequately understood. Here we describe for the first time PLS3 deletions as the underlying cause for childhood-onset primary osteoporosis in 3 boys from 2 families. We carried out thorough clinical, radiological, and bone tissue analyses to explore the consequences of these deletions and to further elucidate the role of PLS3 in bone homeostasis. In family 1, the 2 affected brothers had a deletion of exons 4-16 (NM_005032) in PLS3, inherited from their healthy mother. In family 2, the index patient had a deletion involving the entire PLS3 gene (exons 1-16), inherited from his mother who had osteoporosis. The 3 patients presented in early childhood with severe spinal compression fractures involving all vertebral bodies. The 2 brothers in family 1 also displayed subtle dysmorphic facial features and both had developed a myopathic gait. Extensive analyses of a transiliac bone biopsy from 1 patient showed a prominent increase in osteoid volume, osteoid thickness, and in mineralizing lag time. Results from quantitative backscattered electron imaging and Raman microspectroscopy showed a significant hypomineralization of the bone. Together our results indicate that PLS3 deletions lead to severe childhood-onset osteoporosis resulting from defective bone matrix mineralization, suggesting a specific role for PLS3 in the mineralization process. © 2017 American Society for Bone and Mineral Research.

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort.

BACKGROUND: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. METHODS: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. RESULTS: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (-1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. CONCLUSION: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.

Sun Exposure and Protection Habits in Pediatric Patients with a History of Malignancy.

BACKGROUND: Survivors of childhood cancer are at high risk for developing non-melanoma skin cancer and therefore are firmly advised to avoid or minimize sun exposure and adopt skin protection measures. We aimed to compare sun exposure and protection habits in a cohort of pediatric patients with a history of malignancy to those of healthy controls. METHODS: Case-control study of 143 pediatric patients with a history of malignancy (aged 11.2±4.6 y, Male = 68, mean interval from diagnosis 4.4±3.8 y) and 150 healthy controls (aged 10.4±4.8 y, Male = 67). Sun exposure and protection habits were assessed using validated questionnaires. RESULTS: Patients and controls reported similar sun exposure time during weekdays (94±82 minutes/day vs. 81±65 minutes/day; p = 0.83), while during weekends patients spent significantly less time outside compared to controls (103±85 minutes/day vs. 124±87 minutes/day; p = 0.02). Time elapsed from diagnosis positively correlated with time spent outside both during weekdays (r = 0.194, p = 0.02) and weekends (r = 0.217, p = 0.01), and there was a step-up in sun exposure starting three years after diagnosis. There was no significant difference regarding composite sun protection score between patients and controls. Age was positively correlated with number of sunburns per year and sun exposure for the purpose of tanning, and was negatively correlated with the use of sun protection measures. CONCLUSIONS: Although childhood cancer survivors are firmly instructed to adopt sun protection habits, the adherence to these instructions is incomplete, and more attention should be paid to improve these habits throughout their lives. Since sunlight avoidance may results in vitamin D deficiency, dietary supplementation will likely be needed.

Cognitive and developmental outcome of conservatively treated children with congenital hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants. Its management can be extremely complicated, and may involve medical therapy and surgery. The mainstay of the treatment is to maintain normoglycemia, since hypoglycemia during infancy can have severe neurological consequences. OBJECTIVE: To assess the cognitive and developmental levels and the adaptive skills achieved by children with CHI who were treated medically over the past decade. SUBJECTS AND METHODS: Fourteen children with CHI, under the age of 10 years, who received medical treatment only, underwent a physical and neurological examination and standardized assessments that included the Bayley Scale of Infant and Toddler Development, 3rd Edition, or Kaufman Assessment Battery for Children, the Vineland Adaptive Behavior Scales and the Achenbach Child Behavior Checklist (CBCL) parent questionnaire form. RESULTS: Twelve children (86%) achieved normal range scores in the cognitive and development assessments (Bayley Scale of Infant and Toddler Development or Kaufman Assessment Battery for Children). Only two showed cognitive achievements below the normal range. The Vineland questionnaire, which was based on parental report, showed below normal adaptive skills in eight patients (57%). CONCLUSIONS: In contrast to previous studies showing a high prevalence of neurodevelopmental difficulties in children with congenital hyperinsulinism, our study showed normal cognitive achievements in most children. This may be attributed to the earlier recognition and better management of the disease in the past decade.