Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome).
Alessia MicalizziAndrea PorettiMarta RomaniMonia GinevrinoTommaso MazzaChiara AielloGinevra ZanniBastian BaumgartnerRenato BorgattiKnut BrockmannAna CamachoGaetano CantalupoMartin HaeuslerChristiane HikelAndrea KleinGiorgia MandrileEugenio MercuriDietz RatingRomina RomanielloFilippo Maria SantorelliMareike SchimmelLuigina SpacciniSerap TeberArpad von MoersSarah WenteAndreas ZieglerAndrea ZontaEnrico BertiniEugen BoltshauserEnza Maria ValentePublished in: European journal of human genetics : EJHG (2016)
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.
Keyphrases
- copy number
- intellectual disability
- muscular dystrophy
- autism spectrum disorder
- multiple sclerosis
- ejection fraction
- risk assessment
- pulmonary hypertension
- case report
- heart failure
- body composition
- cord blood
- pulmonary arterial hypertension
- pulmonary artery
- transcription factor
- chronic kidney disease
- high intensity
- congenital heart disease
- patient reported outcomes