Akute schlaffe Myelitis bei Kindern im Jahr 2016 – Rückkehr von „Polio“?

Hintergrund: Obwohl die Poliomyelitis weltweit praktisch ausgerottet ist, treten in den letzten Jahren immer wieder Fälle einer polioartigen Erkrankung auf, die durch asymmetrische schlaffe Lähmungen unterschiedlichen Schweregrades gekennzeichnet sind. Methode: Erfasst wurden Kinder, die 2016 in klinischen Zentren in Bayern und in Niedersachsen betreut wurden. Deutschlandweite Häufigkeiten wurden über freiwillige Meldungen an das Robert Koch-Institut geschätzt. Für das gesamte Jahr 2016 wurden dort 16 Fälle registriert. Ergebnisse: In den beteiligten Zentren wurden im Sommer und Herbst 2016 insgesamt 7 Kinder mit akut aufgetretenen schlaffen Lähmungen betreut. Zwei exemplarische Fälle werden beschrieben, die einen milden und einen schweren Verlauf zusammenfassen. Zur raschen Diagnosefindung ist die Kombination aus klinisch-neurologischer Diagnostik sowie Neurophysiologie, Kernspintomographie und gezielter mikrobiologischer Diagnostik entscheidend. Charakteristisch sind kernspintomographisch nachweisbare Schädigungen des Vorderhorns im Rückenmark oder elektrophysiologisch nachweisbare Läsionen als Zeichen der Motoneuron-Schädigung. Ein Erreger ist aus dem Liquor praktisch nie nachweisbar, aber epidemiologische Zusammenhänge sowie der Nachweis von Viren aus Stuhl oder Atemwegssekreten weisen auf Enteroviren als Verursacher hin. Schlussfolgerung: Die Prognose der Erkrankung ist zu Beginn nicht einzuschätzen und gezielte therapeutische Maßnahmen stehen nicht zur Verfügung

Horizontal head titubation in infants with Joubert syndrome: a new finding

AIM Head thrusts are well documented in Joubert syndrome and ocular motor apraxia. We provide a detailed clinical characterization of head titubation in 13 young children with Joubert syndrome. METHOD Detailed characterization of head titubation was assessed by targeted clinical evaluation and/or analysis of videos. RESULTS In 12 of 13 children (eight males, five females; median age 6y, range 2mo-15y) head titubation was first recognized in the first 2 months of age and decreased in severity until spontaneous resolution. In all children, the head titubation was horizontal, high frequency (~3Hz), had small amplitude (5-10°), was never present during sleep, and did not interfere with the neurodevelopment during infancy. In the majority of children, emotion, anxiety, and tiredness were worsening factors for head titubation. INTERPRETATION Head titubation is a benign, early presentation of Joubert syndrome. Head titubation in hypotonic infants should prompt a careful search for Joubert syndrome. Awareness of its occurrence in Joubert syndrome may avoid unnecessary investigations

Comprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum

BACKGROUND: NKX2-1 encodes a transcription factor with large impact on the development of brain, lung and thyroid. Germline mutations of NKX2-1 can lead to dysfunction and malformations of these organs. Starting from the largest coherent collection of patients with a suspected phenotype to date, we systematically evaluated frequency, quality and spectrum of phenotypic consequences of NKX2-1 mutations. METHODS: After identifying mutations by Sanger sequencing and array CGH, we comprehensively reanalysed the phenotype of affected patients and their relatives. We employed electrophoretic mobility shift assay (EMSA) to detect alterations of NKX2-1 DNA binding. Gene expression was monitored by means of in situ hybridisation and compared with the expression level of MBIP, a candidate gene presumably involved in the disorders and closely located in close genomic proximity to NKX2-1. RESULTS: Within 101 index patients, we detected 17 point mutations and 10 deletions. Neurological symptoms were the most consistent finding (100%), followed by lung affection (78%) and thyroidal dysfunction (75%). Novel symptoms associated with NKX2-1 mutations comprise abnormal height, bouts of fever and cardiac septum defects. In contrast to previous reports, our data suggest that missense mutations in the homeodomain of NKX2-1 not necessarily modify its DNA binding capacity and that this specific type of mutations may be associated with mild pulmonary phenotypes such as asthma. Two deletions did not include NKX2-1, but MBIP, whose expression spatially and temporarily coincides with NKX2-1 in early murine development. CONCLUSIONS: The high incidence of NKX2-1 mutations strongly recommends the routine screen for mutations in patients with corresponding symptoms. However, this analysis should not be confined to the exonic sequence alone, but should take advantage of affordable NGS technology to expand the target to adjacent regulatory sequences and the NKX2-1 interactome in order to maximise the yield of this diagnostic effort