Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti–Boltshauser syndrome)

Alessia Micalizzi, Andrea Poretti, Marta Romani, Monia Ginevrino, Tommaso Mazza, Chiara Aiello, Ginevra Zanni, Bastian Baumgartner, Renato Borgatti, Knut Brockmann, Ana Camacho, Gaetano Cantalupo, Martin Haeusler, Christiane Hikel, Andrea Klein, Giorgia Mandrile, Eugenio Mercuri, D. Rating, Romina Romaniello, Filippo Maria SantorelliMareike Schimmel, L. Spaccini, S. Teber, Arpad Von Moers, Sarah Wente, Andreas Ziegler, Andrea Zonta, Enrico Silvio Bertini, Eugen Boltshauser, Enza Maria Valente

Research output: Contribution to journalArticlepeer-review


Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti–Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS. Here we report the detailed clinical, neuroimaging and genetic characterization of 18 PBS patients from 15 unrelated families. Biallelic LAMA1 variants were identified in 14 families (93%). The only non-mutated proband presented atypical clinical and neuroimaging features, challenging the diagnosis of PBS. Sixteen distinct variants were identified, which were all novel. In particular, the frameshift variant c.[2935delA] recurred in six unrelated families on a shared haplotype, suggesting a founder effect. No LAMA1 variants could be detected in 27 probands with different cerebellar dysplasias or non-progressive cerebellar ataxia, confirming the strong correlate between LAMA1 variants and PBS.European Journal of Human Genetics advance online publication, 2 March 2016; doi:10.1038/ejhg.2016.19.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Publication statusAccepted/In press - Mar 2 2016

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


Dive into the research topics of 'Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti–Boltshauser syndrome)'. Together they form a unique fingerprint.

Cite this