Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene.

IMMT gene codes for mitofilin, a mitochondrial inner membrane protein that regulates the morphology of mitochondrial cristae. The phenotype associated with mutations in this gene has not been yet established, but functional studies carried out show that its loss causes a mitochondrial alteration, both in the morphology of the mitochondrial crests and in their function. We present two cousins from an extended highly consanguineous family with developmental encephalopathy, hypotonia, nystagmus due to optic neuropathy. The likely pathogenic homozygous c.895A>G (p.Lys299Glu) variant in the IMMT gene co-segregates with the disease and associates altered mitochondrial cristae observed by electron microscopy.

Extending the clinical phenotype of SPTAN1: From DEE5 to migraine, epilepsy, and subependymal heterotopias without intellectual disability.

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype-phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy; (2) moderate intellectual disability, severe language delay, ataxia and tremor; (3) normal intelligence, chronic migraine, and generalized tonic-clonic seizures. Remarkably, all these patients showed brain MRI abnormalities, being of special interest the subependymal heterotopias detected in the latter patient. Thus we extend the SPTAN1-related phenotypic spectrum, both in its radiological and clinical involvement. Furthermore, after systematic analysis of all the patients so far reported, we noted an excess of male versus female patients (20:9, p = 0.04), more pronounced among the milder phenotypes. Consequently, some protection factor might be suspected among female carriers, which if confirmed should be considered when establishing the pathogenicity of milder genetic variants in this gene.

Lateral-type posterior fossa ependymomas in pediatric population.

BACKGROUND: Lateral-type posterior fossa ependymomas are a well-defined subtype of tumours both clinically and pathologically, with a poor prognosis. Their incidence is low and surgical management is challenging. The objective of the present work is to review our series of lateral-tye posterior fossa ependymomas and compare our results with those of previous series. METHODS: Among 30 cases of ependymoma operated in our paediatric department in the last ten years, we identified seven cases of lateral-type posterior fossa ependymomas. We then performed a retrospective, descriptive study. RESULTS: Mean age of our patients was 3.75 years. 6 cases presented with hydrocephalus. Mean tumour volume at diagnosis was 61 cc. A complete resection was achieved in six cases and a near-total resection in one patient. 5 patients transiently required a gastrostomy and a tracheostomy. Mean follow-up was 58 months. One case progressed along this period and eventually died. 4 cases of hydrocephalus required a ventriculoperitoneal CSF shunt and two were managed with a third ventriculostomy. At last follow-up 4 patients carried a normal life and two displayed a mild restriction according to Lansky´s scale. CONCLUSIONS: The aim of surgical treatment in lateral-type posterior fossa ependymomas is complete resection. Neurological deficits associated to lower cranial nerve dysfunction are common but transient. Deeper genetic characterization of these tumours may identify risk factors that guide stratification of adjuvant therapies.