Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698201
Poster Presentations
Poster Are a GNP Varia 1/CNS Tumours
Georg Thieme Verlag KG Stuttgart · New York

Aicardi-Goutières Syndrome 2 - Case Reports of 2 Siblings

Mirjam Kreuzer
1   Städtisches Klinikum, Klinik für Kinder- und Jugendmedizin, Sozialpädiatrisches Zentrum, Klinik für Kinder- und Jugendmedizin, Karlsruhe, Germany
,
Angela Abicht
2   Medizinisch Genetisches Zentrum (MGZ), Medizinisch Genetisches Zentrum (MGZ), München,Germany
,
Ingeborg Krägeloh-Mann
3   Universitätsklinik für Kinder- und Jugendmedizin, Abteilung für Neuropädiatrie, Entwicklungsneurologie und Sozialpädiatrie, Neuropädiatrie, Entwicklungsneurologie, Sozialpädiatrie, Tübingen,Germany
,
Viola Prietsch
1   Städtisches Klinikum, Klinik für Kinder- und Jugendmedizin, Sozialpädiatrisches Zentrum, Klinik für Kinder- und Jugendmedizin, Karlsruhe, Germany
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Publikationsverlauf

Publikationsdatum:
11. September 2019 (online)

 
 

    Question: Aicardi-Goutières Syndrome (AGS) is an autosomal recessively inherited, early manifesting, rapid progressive encephalopathy with clinical and genetic heterogeneity, which is regarded as underdiagnosed, due to its low incidence and atypical clinical manifestation. 4 genetic variations (AGS 1 – AGS 4) are known. We present two Syrian siblings with the diagnosis of AGS 2 (gene locus 13q14.3).

    Methods: Patient 1, male, born in Syria, presented at the age of 6,5 years with developmental retardation and spasticity, which was regarded as residual condition resulting from a meningitis at the age of 6 months. Until then the patient was reported to have developed normally. Considering the lack of therapeutic consequence further investigations were not performed at that time. Patient 2, sister of patient 1, born in Germany, presented at the age of 6 months because of microcephaly, loss of weight and delayed motor development with hypotonia of the trunk and hypertonia of the extremities.

    Results: The cerebral MRI of patient 2 showed pathological myelination, consistent with hypomyelination, reduced differentiation of grey and white matter, particularly in the frontal region, accentuated inner and outer cerebrospinal fluid spaces and pathological peaks of choline and lactate in spectroscopy. The analysis of the cerebrospinal fluid detected a slightly increased cell count of 20/µl (lympho-monocytic). Subsequently a cerebral MRI was performed in patient 1, which showed a myelination disorder, particularly located in the frontal subcortical region, concerning the U-fibres. Additionally signal abnormalities of the brainstem and a pathological peak of lactate in spectroscopy were also detected. A common genetic basis was presumed despite the different patterns of abnormal myelination. As clinical examination, brain imaging and comprehensive metabolic analysis did not result in an explicit classification, the blood of patient 2 was analyzed by next- generation sequencing leukodystrophy panels, detecting the pathogen homozygous variation c.554T>G (p.Val185Gly), compatible with a RNaseH2B- associated AGS 2. The identical pathogen variation was determined in patient 1.

    Discussion: Retrospectively the initial suspected diagnosis of meningitis/encephalitis in patient 1 might have resulted from the characteristic cerebrospinal fluid pleocytosis in AGS 2. Pathognomonic intracranial calcifications could not be verified, as no cranial computer tomography was performed.

    Conclusion: The clinical presentation of AGS shows heterogeneity in clinical symptoms and the pattern of abnormal myelination. There is evidence to assume that the phenotypical spectrum will expand due to genetic screening, as reported in this case.


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