Not Only Diagnostic Yield: Whole-Exome Sequencing in Infantile Cardiomyopathies Impacts on Clinical and Family Management.

Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio (proband and parents)-WES to determine whether results contributed to clinical management in urgent and non-urgent settings. Twenty-nine out of 42 enrolled patients (69.0%) received a definitive molecular diagnosis. The mean time-to-diagnosis was 9.7 days in urgent settings, and 17 out of 24 patients (70.8%) obtained an etiological classification. In non-urgent settings, the mean time-to-diagnosis was 225 days, and 12 out of 18 patients (66.7%) had a molecular diagnosis. In 37 out of 42 patients (88.1%), the genetic findings contributed to clinical management, including heart transplantation, palliative care, or medical treatment, independent of the patient's critical condition. All 29 patients and families with a definitive diagnosis received specific counseling about recurrence risk, and in seven (24.1%) cases, the result facilitated diagnosis in parents or siblings. In conclusion, genetic diagnosis significantly contributes to patients' clinical and family management, and trio-WES should be performed promptly to be an essential part of care in infantile cardiomyopathy, maximizing its clinical utility.

Phenotypic spectrum of short-chain enoyl-Coa hydratase-1 (ECHS1) deficiency.

INTRODUCTION: ECHS1 encodes for short-chain enoyl-CoA hydratase, a key component in b-oxidation. This enzyme is also involved in the isoleucine and valine catabolic pathways. The literature contains reports of scattered cases of ECHS1 mutation, which show a wide clinical spectrum of presentation. Despite that the clinical spectrum of the disease has not been defined so far due to the absence of previous systematic reviews and descriptions of large series of patients. METHODS: We performed a systematic literature review of so far reported ECHS1 mutated patients and we reported two additional cases. We pointed out clinical and neuroradiological features of all patients. RESULTS: 45 patients were included in the analysis. Based on clinical and neuroradiological feature we were able to distinguish four main phenotypes of ECHS1deficiency: a severe neonatal presentation with a rapid and fatal course and significant white matter abnormalities; a severe infantile variant with slower neurological deterioration, developmental delay, pyramidal and extrapyramidal signs, optic atrophy, feeding difficulties, and degeneration of the deep gray nuclei; a slowly progressive infantile form, qualitatively similar to the previous phenotype, but less severe with mainly basal ganglia involvement; and a final phenotype, present in only few cases, characterized by paroxysmal exercise-induced dystonic attacks, normal neurological examination between these episodes, and isolated pallidal degeneration on MRI. INTERPRETATION: ECHS1 mutations cause metabolic encephalopathy with a wide range of clinical presentations that can be grouped into four main phenotypes, each with a distinct profile in terms of severity on clinical presentation, disease course and MRI involvement.

Two cases of neonatal human parechovirus 3 encephalitis.

We report 2 neonates with human parechoviruses type 3 encephalitis. Both newborns presented with fever, irritability and seizures. Cerebrospinal fluid analyses were normal, but magnetic resonance imaging revealed white matter damage, suggesting human parechoviruse infection. Human parechoviruses type 3-RNA was detected in cerebrospinal fluid samples and in blood, stool, urine and respiratory samples, indicating the dissemination of the virus.

Teaching neuroimages: neonatal parechovirus encephalitis: typical MRI findings.

A full-term 9-day-old girl presented with fever, irritability, and seizures. The routine CSF examination, cranial ultrasound, and laboratory tests were normal. Brain MRI showed diffuse white matter abnormality (figure). Human parechovirus (HPeV) type 3 was isolated in both CSF and blood. The neurodevelopmental outcome at 4 months is poor, and MRI shows an extensive cystic leukomalacia in the frontal white matter.

Fusobacterium nucleatum endocarditis mimicking polymyalgia rheumatica.

A case of Fusobacterium nucleatum endocarditis in an 80-year-old man is reported. The patient presented with a headache and nonspecific musculoskeletal symptoms and was misdiagnosed as having polymyalgia rheumatica. The diagnosis of bacterial endocarditis was delayed because of an insidious presentation, typical in infections with low virulence micro-organisms. The musculoskeletal symptoms, unresponsive to protracted corticosteroids, completely resolved with intravenous ampicillin treatment. Rheumatologic symptoms may hinder the correct diagnosis of subacute infective endocarditis. An atypical evolution of a common rheumatic disorder such as polymyalgia rheumatica should alert physicians to the possibility of bacterial endocarditis.