Identification of a novel mutation in FGFR1 gene in mother and daughter with Kallmann syndrome.

OBJECTIVES: Congenital hypogonadotropic hypogonadism combined with anosmia or hyposmia is considered Kallmann syndrome (KS). It is often accompanied by bone defects. CASE PRESENTATION: Here, we report a girl and her mother with KS caused by a novel mutation in the fibroblast growth factor receptor 1 gene (FGFR1). Interestingly, the daughter presented syndactyly and oligodactyly of the feet. CONCLUSIONS: The presence of bone malformations in a KS patient should direct the geneticist towards a search for specific mutations in FGFR1. Our finding contributes to enrich the spectrum of FGFR1 mutations in patients with KS.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67-14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic; 14 suffered accidental excision of some parathyroid gland, but none more than two of them; 12 presented HP, of which 3 were permanent; 5 presented clinical symptoms; 1 of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (p = 0.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (p = 0.29). The three cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (p = 0.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital. / Hipoparatiroidismo postiroidectomía: experiencia de 20 años en un hospital infantil.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67 to 14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic. Fourteen suffered accidental excision of some parathyroid gland, but none more than t2 of them. Twelve presented HP, of which 3 were permanent; 5 presented clinical symptoms; one of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (P=.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (P=.29). The 3 cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (P=.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Rare Germline DICER1 Variants in Pediatric Patients With Cushing's Disease: What Is Their Role?

Context: The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the DICER1 gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD). The role of DICER1 in other corticotropinomas, however, remains unknown. Objective: To perform a comprehensive screening for DICER1 variants in a large cohort of CD patients, and to analyze their possible contribution to the phenotype. Design, setting, patients, and interventions: We included 192 CD cases: ten young-onset (age <30 years at diagnosis) patients were studied using a next generation sequencing panel, and 182 patients (170 pediatric and 12 adults) were screened via whole-exome sequencing. In seven cases, tumor samples were analyzed by Sanger sequencing. Results: Rare germline DICER1 variants were found in seven pediatric patients with no other known disease-associated germline defects or somatic DICER1 second hits. By immunohistochemistry, DICER1 showed nuclear localization in 5/6 patients. Variant transmission from one of the parents was confirmed in 5/7 cases. One patient had a multinodular goiter; another had a family history of melanoma; no other patients had a history of neoplasms. Conclusions: Our findings suggest that DICER1 gene variants may contribute to the pathogenesis of non-syndromic corticotropinomas. Clarifying whether DICER1 loss-of-function is disease-causative or a mere disease-modifier in this setting, requires further studies. Clinical trial registration: ClinicalTrials.gov: NCT00001595.