LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance.

This study focused on the molecular characterization of patients with leukoencephalopathy associated with a specific biochemical defect of mitochondrial respiratory chain complex III, and explores the impact of a distinct magnetic resonance imaging pattern of leukoencephalopathy to detect biallelic mutations in LYRM7 in patients with biochemically unclassified leukoencephalopathy. 'Targeted resequencing' of a custom panel including genes coding for mitochondrial proteins was performed in patients with complex III deficiency without a molecular genetic diagnosis. Based on brain magnetic resonance imaging findings in these patients, we selected additional patients from a database of unclassified leukoencephalopathies who were scanned for mutations in LYRM7 by Sanger sequencing. Targeted sequencing revealed homozygous mutations in LYRM7, encoding mitochondrial LYR motif-containing protein 7, in four patients from three unrelated families who had a leukoencephalopathy and complex III deficiency. Two subjects harboured previously unreported variants predicted to be damaging, while two siblings carried an already reported pathogenic homozygous missense change. Sanger sequencing performed in the second cohort of patients revealed LYRM7 mutations in three additional patients, who were selected on the basis of the magnetic resonance imaging pattern. All patients had a consistent magnetic resonance imaging pattern of progressive signal abnormalities with multifocal small cavitations in the periventricular and deep cerebral white matter. Early motor development was delayed in half of the patients. All patients but one presented with subacute neurological deterioration in infancy or childhood, preceded by a febrile infection, and most patients had repeated episodes of subacute encephalopathy with motor regression, irritability and stupor or coma resulting in major handicap or death. LYRM7 protein was strongly reduced in available samples from patients; decreased complex III holocomplex was observed in fibroblasts from a patient carrying a splice site variant; functional studies in yeast confirmed the pathogenicity of two novel mutations. Mutations in LYRM7 were previously found in a single patient with a severe form of infantile onset encephalopathy. We provide new molecular, clinical, and neuroimaging data allowing us to characterize more accurately the molecular spectrum of LYRM7 mutations highlighting that a distinct and recognizable magnetic resonance imaging pattern is related to mutations in this gene. Inter- and intrafamilial variability exists and we observed one patient who was asymptomatic by the age of 6 years.

Variante faringo-cérvico-braquial da síndrome de Guillain-Barré:uma causa rara de disfunção bulbar aguda em crianças / Pharyngeal-cervical-brachial variant of Guillain-Barré syndrome:a rare cause of acute bulbar dysfunction in children

Aims: To report a case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome, which is characterized by rapidly progressivebulbar palsy with upper limb, neck and oropharyngeal involvement. It is a rare disorder in childhood and most cases have been described inadolescents.Case Description: A seven year-old-boy presented with dysarthria, hoarseness, dysphagia, facial diplegia and bilateral progressive upperlimb weakness. These symptoms started two weeks after a gastrointestinal infection. Nerve conduction studies were compatible with an acutedemyelinating polyneuropathy in the upper extremities. Anti-ganglioside antibodies in the serum (anti-GT1a, GD1a, GQ1b) were positiveand Campylobacter jejuni was isolated from stools. The patient was treated with intravenous immunoglobulin and needed ventilatory supportduring the first 12 days of admission. He was discharged at day 15 showing improvement of his neurological deficits. He fully recovered aftereleven months of follow-up.Conclusions: Although pharyngeal-cervical-brachial variant of Guillain-Barré syndrome is uncommon in children, it should be consideredin a child with acute bulbar dysfunction because a timely diagnosis allows the early institution of therapeutic measures that can be lifesaving.

Objetivos: Relatar um caso da variante faringo-cervico-braquial da síndrome de Guillain-Barré, que se caracteriza por paralisia bulbarrapidamente progressiva com envolvimento dos membros superiores, pescoço e região orofaríngea. É um diagnóstico raro na criança, ocorrendoa maioria dos casos em adolescentes.Descrição do Caso: Um menino de sete anos de idade iniciou com queixas de disartria, disfonia, disfagia, diplegia facial e fraqueza muscularprogressiva dos membros superiores. Estes sintomas surgiram duas semanas após uma infeção gastrointestinal. Os estudos eletrofisiológicosforam compatíveis com polineuropatia aguda desmielinizante nos membros superiores. Os anticorpos anti-gangliosídeo no plasma(anti-GT1a, GD1a, GQ1b) foram positivos e Campylobacter jejuni foi isolado nas fezes. O paciente foi tratado com imunoglobulina endovenosae necessitou de suporte ventilatório durante os primeiros 12 dias. Teve alta no 15º dia com melhora dos sintomas neurológicos. Recuperou-setotalmente após 11 meses de seguimento.Conclusões: Apesar da variante faringo-cervico-braquial ser pouco frequente em idade pediátrica, é um diagnóstico que deve ser consideradoperante uma criança com disfunção bulbar aguda, pois a identificação precoce permite instituir rapidamente medidas terapêuticas que podemevitar a morte.

[Peutz-Jeghers syndrome: variability of gastrointestinal expression at pediatric age]. / Sindrome de Peutz-Jeghers. Diversidade de expressão gastrointestinal em idade pediátrica e considerações sobre a sua abordagem clínica.

Peutz-Jeghers syndrome is a rare autosomal dominant condition, characterized by gastrointestinal polyposis, mucocutaneous pigmentation and high risk of neoplasia in multiple organs. At pediatric age, major clinical impact is related to complications associated to intestinal polyps, but neoplasic risk isn't negligible. Though clinical surveillance is recommended since the age of 10 years, relevant lesions may occur before that age. Conventional radiology and endoscopy have recognized limitations at this age group, and new diagnostic and intervention tools, such as video-capsule and per-operative enteroscopy, are not yet widely used. We present 5 pediatric cases (age under 10 years) with diversity of gastrointestinal expression (including one case with histologic evidence of dysplasia in a large colonic polyp), emphasizing the need of specific guidelines concerning young children.