In vivo magnetic resonance spectroscopy for the differential diagnosis of a cerebral mass in a boy with precocious puberty: a case report and review of the literature.

PURPOSE: To highlight the role of in vivo magnetic resonance spectroscopy (MRS) as a non-invasive tool that can clarify the etiology of sellar tumors by presenting the case of a boy with central precocious puberty (CPP) and to review the current literature. METHODS: A 4-year-old boy was admitted to our hospital due to repeated episodes of focal and gelastic seizures in the previous year. Clinical examination (testicular volume 4-5 ml bilaterally, penile length of 7.5 cm, and absence of axillary or pubic hair) and laboratory tests (FSH, LH, and testosterone) were indicative of CPP. The combination of gelastic seizures with CPP in a 4-year-old boy raised the suspicion of hypothalamic hamartoma (HH). Brain MRI revealed a lobular mass in the suprasellar-hypothalamic region. The differential diagnosis included glioma, HH, and craniopharyngioma. To further investigate the CNS mass, an in vivo brain MRS was performed. RESULTS: Οn conventional MRI, the mass demonstrated isointensity to gray matter on T1 weighted images but slight hyperintensity on T2-weighted images. It did not show restricted diffusion or contrast enhancement. On MRS, it showed reduced N-acetyl aspartate (NAA) and slightly elevated myoinositol (MI) compared with values in normal deep gray matter. The MRS spectrum, in combination with the conventional MRI findings, were consistent with the diagnosis of a HH. CONCLUSION: MRS is a state-of-the-art, non-invasive imaging technique that compares the chemical composition of normal tissue to that of abnormal regions by juxtaposing the frequency of measured metabolites. MRS, in combination with clinical evaluation and classic MRI, can provide identification of CNS masses, thus eliminating the need for an invasive biopsy.

Combined exome analysis and exome depth assessment achieve a high diagnostic yield in an epilepsy case series, revealing significant genomic heterogeneity and novel mechanisms.

OBJECTIVES: Genetics of epilepsy are highly heterogeneous and complex. Lesions detected involve genes encoding various types of channels, transcription factors, and other proteins implicated in numerous cellular processes, such as synaptogenesis. Consequently, a wide spectrum of clinical presentations and overlapping phenotypes hinders differential diagnosis and highlights the need for molecular investigations toward delineation of underlying mechanisms and final diagnosis. Characterization of defects may also contribute valuable data on genetic landscapes and networks implicated in epileptogenesis. METHODS: This study reports on genetic findings from exome sequencing (ES) data of 107 patients with variable types of seizures, with or without additional symptoms, in the context of neurodevelopmental disorders. RESULTS: Multidisciplinary evaluation of ES, including ancillary detection of copy number variants (CNVs) with the ExomeDepth tool, supported a definite diagnosis in 59.8% of the patients, reflecting one of the highest diagnostic yields in epilepsy. CONCLUSION: Emerging advances of next-generation technologies and 'in silico' analysis tools offer the possibility to simultaneously detect several types of variations. Wide assessment of variable findings, specifically those found to be novel and least expected, reflects the ever-evolving genetic landscape of seizure development, potentially beneficial for increased opportunities for trial recruitment and enrollment, and optimized, even personalized, medical management.

Novel Hemizygous Missense Variant of Spermine Synthase (SMS) Gene Causes Snyder-Robinson Syndrome in a Four-Year-Old Boy.

Snyder-Robinson syndrome (SRS) is an extremely rare X-linked intellectual disability syndrome (MRXSSR; MIM #309583). The main clinical features of SRS include psychomotor delay, hypotonia, and asthenic-type body habitus - reduced body weight and bone abnormalities (osteoporosis, fractures, kyphoscoliosis). We report a case of SRS with a hemizygous missense variant in the SMS gene,c.334C>G (p.Pro112Ala), in a 4-year-old boy, who initially developed hypotonia, delayed motor skills, and subsequently epilepsy. This variant in SMS was found to be de novo. To the best of our knowledge, this novel SMS gene variant has never been previously reported in disease-related variation databases, such as ClinVar or HGMD.

A novel de novo KCNQ2 mutation in a child with treatmentresistant early-onset epileptic encephalopathy.

Benetou C, Papailiou S, Maritsi D, Anagnostopoulou K, Kontos H, Vartzelis G. A novel de novo KCNQ2 mutation in a child with treatmentresistant early-onset epileptic encephalopathy. Turk J Pediatr 2019; 61: 279-281. Mutations in KCNQ2 gene, encoding for voltage-gated K+ channel subunit, may result in a wide spectrum of early-onset epileptic disorders. The phenotype of the disease varies from `benign familial neonatal seizures` to `severe epileptic encephalopathies`. In this report, we present a novel mutation [namely: c.683A > G (p.His228Arg)], as a presumable cause of severe infantile-onset neonatal seizures, in a 3-month old boy. The seizures have been poorly responsive to various pharmacological treatments, with phenytoin and carbamazepine presenting with the most favourable results so far. The study of our patient could help to further clarify the clinical manifestations of KCNQ2 mutations, revealing a previously unreported mutation.