Six Novel Variants in the MKRN3 Gene Causing Central Precocious Puberty.

peer reviewed[en] CONTEXT: Idiopathic central precocious puberty (iCPP) is defined by the premature reactivation of the hypothalamic-pituitary-gonadal axis with normal magnetic resonance imaging scan of the central nervous system, causing the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys. MKRN3 loss of function variants now represent the most common genetic cause of iCPP. OBJECTIVE: This work aims to document the clinical course of puberty in 8 families harboring pathogenic MKRN3 variants. METHODS: This is an observational case series study of patients with CPP due to MKRN3 variants followed in a single center. RESULTS: Genetic analysis of MKRN3 was carried out in 28 unrelated patients with iCPP and a family history of paternal inheritance or no/unavailable maternal inheritance, particularly in case of very early and rapidly evolving CPP. We identified 6 novel and 2 recently described variants in the MKRN3 gene in 9 girls, 1 boy, and their family members. These mutations were all predicted to be deleterious by in silico prediction programs. CONCLUSION: We have identified 6 novel MKRN3 mutations in children with CPP. An MKRN3 loss of function should be considered after careful history pinpointing paternally inherited CPP. A family segregation study allowed the detection of an MKRN3 variant in 2 young brothers still prepubertal, raising the question of screening and management of asymptomatic prepubertal family members

Acute pancreatitis as initial presentation for hereditary spherocytosis: A case report

Hereditary spherocytosis is a common cause for hemolytic anemia but clinical presentation can be misleading. We suggest that this diagnosis should be evocated in children presenting with acute unexplained jaundice that can be associated with acute pancreatitis

ROHHAD(NET) Syndrome: Systematic review of the clinical timeline and recommendations for diagnosis and prognosis.

peer reviewedCONTEXT: Rapid onset Obesity with Hypothalamic dysfunction, Hypoventilation, Autonomic Dysregulation and Neural Tumor Syndrome (ROHHHAD(NET)) is a rare and potentially fatal disease. No specific diagnostic biomarker is currently available, making prompt diagnosis challenging. Since its first definition in 2007, a complete clinical analysis leading to specific diagnosis and follow-up recommendations is still missing. OBJECTIVE: To describe the clinical timeline of symptoms of ROHHAD(NET) and propose recommendations for diagnosis and follow-up. DESIGN: We conducted a systematic review of all ROHHAD(NET) case studies and report a new ROHHAD patient with early diagnosis and multidisciplinary care. METHODS: All the articles that meet the definition of ROHHAD(NET) and provide chronological clinical data were reviewed according to the PRISMA individual patient data (IPD) guidelines. The data were grouped into 7 categories: hypothalamic dysfunction, autonomic dysregulation, hypoventilation, NET, psychiatric symptoms, other clinical manifestations, outcome. RESULTS: 43 IPD were analyzed. The timeline of the disease shows rapid onset obesity followed shortly afterwards by hypothalamic dysfunction. Dysautonomia was reported at a median age of 4.95 years and hypoventilation at 5.33 years, or 2,2 years after the initial obesity. A NET was reported in 56% of the patients and 70% of these tumors were diagnosed within 2 years after initial weight gain. CONCLUSION: Since early diagnosis improves the clinical management and the prognosis in ROHHAD(NET), this diagnosis should be considered for any child with a rapid and early obesity. We propose guidance for systematic follow-up and advise multidisciplinary management with the aim of improving prognosis and life expectancy