Background Pontocerebellar hypoplasia (PCH) is a rare group of disorders mainly affecting the cerebellum and pons. Supratentorial structures are variably involved. We assessed brain growth patterns... Show moreBackground Pontocerebellar hypoplasia (PCH) is a rare group of disorders mainly affecting the cerebellum and pons. Supratentorial structures are variably involved. We assessed brain growth patterns in patients with the most frequent forms of PCH, namely PCH1B (OMIM#614678) and PCH2A (OMIM#277470), since in these types of PCH, pre- and postnatal neurodegeneration is established by neuropathological profiling. To assess the influence of the different pathomechanisms on postnatal growth patterns, we included CASK- associated microcephaly and PCH (MICPCH, OMIM#300749) patients in our analyses, as MICPH mimics PCH on magnetic resonance imaging (MRI) but represents a developmental disorder including abnormal neuronal migration.Methods A total of 66 patients were included: 9 patients with PCH1B, 18 patients with PCH2A, 6 patients with MICPCH, and 33 age- and gender-matched hospital-based controls. Segmentation of the vermis and cerebellum was performed manually, as were measurements of the thickness of the head of the caudate nucleus, the width of the anterior horn, and lateral ventricle size.Results The cerebellum was severely hypoplastic at birth in all patients, and postnatal growth was nearly absent. In patients with PCH1B/2A, we found relative sparing of the vermis compared with the cerebellar hemispheres. In addition, PCH1B and PCH2A cases demonstrated thinning of the head of the caudate nucleus, an associated increase in anterior horn width, and an increase in lateral ventricle size. None of these features were seen in the MICPCH group.Conclusions Our findings confirm the progressive nature including caudate nucleus atrophy in PCH1B and PCH2A. In MICPCH, the relative sparing of supratentorial structures confirms its different pathomechanism. Show less
IJzerman, N.S.; Drabbe, C.; Hollander, D. den; Mohammadi, M.; H. van boven; Desar, I.M.E.; ... ; Graaf, W.T.A. van der 2020
Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and... Show moreGastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks KIT/PDGFR mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown. We therefore aimed to describe the clinical, pathological and molecular characteristics of GIST in in YA. YA GIST patients registered in the Dutch GIST Registry (DGR) were included, and data were compared to those of older adults (OA). From 1010 patients in the DGR, 52 patients were YA (54% male). Main tumour locations were stomach (46%) and small intestine (46%). GIST genetic profiles were mutations in KIT (69%), PDGFRA (6%), SDH deficient (8%), NF1 associated (4%), ETV6-NTRK3 gene fusion (2%) or wildtype (10%). Statistically significant differences were found between the OA and YA patients (localisation, syndromic and mutational status). YA presented more often than OA in an emergency setting (18% vs. 9%). The overall five-year survival rate was 85%. In conclusion, YA GISTs are not similar to typical adult GISTs and also differ from paediatric GISTs, as described in the literature. In this series, we found a relatively high percentage of small intestine GIST, emergency presentation, 25% non-KIT/PDGFRA mutations and a relatively good survival. Show less
Weeghel, C. van; Wierenga, A.P.A.; Versluis, M.; Hall, T. van; Velden, P.A. van der; Kroes, W.G.M.; ... ; Jager, M.J. 2019
