CNP deficiency causes severe hypomyelinating leukodystrophy in humans.

Myelin pathologies are an important cause of multifactorial, e.g., multiple sclerosis, and Mendelian, e.g., leukodystrophy, neurological disorders. CNP encodes a major component of myelin and its CNS expression is exclusive to myelin-forming oligodendrocytes. Deficiency of CNP in mouse causes a lethal white matter neurodegenerative phenotype. However, a corresponding human phenotype has not been described to date. Here, we describe a multiplex consanguineous family from Oman in which multiple affected members display a remarkably consistent phenotype of neuroregression with profound brain white matter loss. A novel homozygous missense variant in CNP was identified by combined autozygome/exome analysis. Immunoblot analysis suggests that this is a null allele in patient fibroblasts, which display abnormal F-actin organization. Our results suggest the establishment of a novel CNP-related hypomyelinating leukodystrophy in humans.

The impact of 18F-FDG PET on initial staging and therapy planning of pediatric soft-tissue sarcoma patients.

BACKGROUND: Soft-tissue sarcomas in children are a histologically heterogenous group of malignant tumors accounting for approximately 7% of childhood cancers. There is a paucity of data on the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for initial staging and whether PET influenced management of these patients. OBJECTIVE: The aim of this analysis is to assess the use of 18F-FDG PET exclusively, and as a supplement to cross-sectional imaging in comparison to typical imaging protocols (CT and magnetic resonance imaging [MRI]) for initial staging as well as therapy planning in pediatric soft-tissue sarcoma patients. MATERIALS AND METHODS: The list of 18F-FDG PET/CT performed for soft-tissue sarcoma between March 2007 and October 2017 was obtained from the Hospital Information System database. Twenty-six patients who had received 18F-FDG PET, MRI and/or CT at initial diagnosis were included in the study. 18F-FDG PET and concurrent diagnostic CT and MRI at initial staging were independently reviewed to note the number of primary and metastatic lesions detected by each modality. A chart review was conducted to collect information on final diagnosis, staging and treatment plan. RESULTS: During the study period, 26 patients (15 females) ages 1.3-17.9 years (median age: 6 years) had received 18F-FDG PET/CT at initial diagnosis of soft-tissue sarcoma. Diagnostic CT was available for comparison in all 26 patients and MRI was available in 18 patients. The mean interval between cross-sectional imaging and 18F-FDG PET was 5.9 days (range: 0-30 days). All 26 primary lesions were equally detected by 18F-FDG PET compared to CT and MRI. From 84 metastatic lesions, 16 were detected by PET as well as CT and MRI, 12 by 18F-FDG PET only (included mainly lymph node metastases) and 56 by CT and MRI only (included mainly lung metastases). 18F-FDG PET changed therapy planning in 5 patients out of 26 (19%) by showing additional lesions not detected by CT and MRI. CONCLUSION: 18F-FDG PET proved to be a valuable tool for precise initial staging of pediatric soft-tissue sarcoma patients, especially in detecting lymph node metastasis, and could be included in their initial work-up. Given the relative rarity and heterogeneity of this group of tumors, additional investigations are required to definitely establish a role for 18F-FDG PET in the initial staging and therapy planning of soft-tissue sarcoma in the pediatric population.

Secondary intracranial hypertension in aplastic anemia: A case report and review of current concepts.

Intracranial hypertension (IH) when detected mandates prompt and appropriate therapy to avoid permanent visual impairment. We report a 7-year-old boy who presented to the emergency services with purpuric rashes and bruises. Peripheral blood smear and bone marrow aspiration confirmed the diagnosis of aplastic anemia. During admission, the child developed headache, nausea, vomiting, and diplopia. Ophthalmic examination revealed intermittent esotropia and bilateral papilledema. The findings on neuroimaging and lumbar puncture led to the diagnosis of secondary IH (SIH). The intracranial pressure normalized on treatment with oral acetazolamide, oral furosemide, and intravenous dexamethasone.

A Novel Splice-Site Variant in SLC12A6 Causes Andermann Syndrome without Agenesis of the Corpus Callosum.

Andermann syndrome, otherwise known as agenesis of the corpus callosum with peripheral neuropathy (ACCPN), is an autosomal recessive motor and sensory neuropathy known to be associated with ACC and mild-to-moderate intellectual disability. We present a 7-year-old girl with infantile-onset hypotonia, mild intellectual disability, and severe motor and sensory demyelinating peripheral neuropathy. Brain magnetic resonance imaging showed intact corpus callosum. Whole exome sequencing showed a novel splice-site pathogenic variant in the SLC12A6 gene. We confirm that ACC is not a mandatory feature and suggest that the term ACCPN may be misleading.