A novel CHD3 variant in a patient with central precocious puberty: Expanded phenotype of Snijders Blok-Campeau syndrome?

Snijders Blok-Campeau syndrome is an autosomal dominant genetic disorder first described in 2018, mostly associated with de novo variants in the CHD3 gene that affects chromatin remodeling. This syndrome is characterized by developmental delay, speech delay, and intellectual disability, but only about 60 affected individuals have been reported to date. We report a de novo likely pathogenic CHD3 variant (c.5609G > A; p. (Arg1870Gln)) in a young female presenting with features of Snijders Blok-Campeau syndrome including speech delay, autism spectrum disorder, learning difficulties, characteristic facial dysmorphisms, and a feature not previously described in this syndrome, idiopathic central precocious puberty. Her puberty was controlled with monthly injections of a GnRH analogue. Targeted exome sequencing was negative for genes known to be responsible for central precocious puberty. Our case raises the possibility that variants in CHD3 gene may also result in central precocious puberty. Strengthening this association could expand the phenotypic spectrum of the Snijders Blok-Campeau syndrome and should be included in multigene panels for precocious puberty.

Is Gadolinium Contrast Necessary for Pituitary MRI in the Evaluation of Pediatric Short Stature and Growth Hormone Deficiency?

INTRODUCTION: Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone deficiency (GHD) is a commonly considered etiology. Brain and pituitary magnetic resonance imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the most widely used imaging in assessing patients with GHD. Given the significant strides made in MRI technology, the need for contrast material should be reassessed. METHOD: We performed a retrospective review of healthy patients with short stature and/or GHD who underwent brain and pituitary MRI with and without contrast to assess the added value of contrast administration. RESULTS: 227/318 identified patients underwent growth hormone (GH) stimulation testing; 28 (12.3%) with normal GH response and 62 (27.3%) with severe GHD. We found a low incidence of sellar and suprasellar pathologies. When comparing noncontrast and contrast MRI, we found perfect agreement in detecting abnormal posterior pituitary bright spots (kappa:1.0) and substantial agreement in detecting pars intermedia cysts and posterior superior sellar cysts (kappa: 0.74 and 0.71, respectively). Initially, only moderate agreement was found in detecting infundibular abnormalities (kappa: 0.51), although a revised noncontrast MRI protocol with high-resolution 3D images enabled visualization of the infundibulum. CONCLUSION: The MRI evaluation of healthy patients with short stature and/or isolated GHD may be completed without the use of GBCAs. The slight overestimation of pituitary stalk interruption by noncontrast images can be overcome by adding newer high-resolution sequences.

Refractory hypoglycemia in a pediatric patient with desmoplastic small round cell tumor.

Background Tumor-induced hypoglycemia is a rare and serious complication that is usually a consequence of either excessive insulin secretion (insulinoma) or because of non-islet cell tumor hypoglycemia (NICTH). NICTH is a rare phenomenon seen most often in adult patients. It is associated with different tumor types. Here, we report the first case to the best of our knowledge in the literature of a pediatric patient with NICTH associated with desmoplastic small round cell tumor (DSRT). Case presentation This is a 15-year-old girl who presented with symptomatic hypoglycemia and abdominal mass. She required an intravenous glucose infusion rate as high as 9 mg/kg/min in addition to glucose containing oral supplements in order to maintain her blood glucose above 60 mg/dL. Computed tomography (CT) scan of the chest, abdomen and pelvis showed multiple hepatic lesions with an intraperitoneal soft tissue mass which subsequently was diagnosed as DSRT. When the blood glucose was 45 mg/dL, the insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were suppressed with an appropriate elevation of cortisol. Subsequently, an insulin-like growth factor-2 (IGF-2) level was sent and the IGF-2:IGF-1 ratio was found to be elevated >10 consistent with NICTH. After the first dose of chemotherapy, hypoglycemia improved, and she was weaned off glucose containing fluids. Conclusions NICTH should be considered in all cancer patients regardless of their age with refractory hypoglycemia.