Short title of the study
Mild forms of tubulinopathies
Targeted gene(s)/phenotype/disorder under study
Summary (1000 letters max):
Tubulinopathies define a group of congenital neurodevelopmental disorders caused by pathogenic variants in genes encoding different isotypes of tubulin. The most common congenital brain malformations found in tubulinopathies are cerebral cortical anomalies (lissencephaly, polymicrogyrie), poorly defined basal ganglia owing to ectopic corticospinal tract, anomalies of the corpus callosum, and vermian or brainstem hypoplasia/dysgenesis. Clinically, most patients have global developmental delay, moderate to severe intellectual disability, with or without seizures and motor troubles.
It is becoming clear that some patients do not have a severe phenotype, including fetuses with subtle brain anomalies. Some of these variants may be inherited from mildly or a- symptomatic parents. This raises the issue of the long-term prognosis and/or prenatal counselling.
To increase our knowledge on tubulinopathies with mild neurological phenotypes, we would like to collect clinical and MRI data of 1)adults or children over 6 years, 2) carrying a pathogenic variant in TUBA1A, TUBB2B, TUBB3, TUBB2A or TUBG1, 3) with an atypical phenotype, ie a milder clinical phenotype from normal cognition to mild intellectual disability
Our aim is to delineating the phenotype and long-term prognosis of these « mild forms of tubulinopathies » to improve genetic/prenatal counselling.
Institution (dept, hospital, City)
GHEP Hôpital Trousseau, Sorbonne Université.
Specific requirements beyond clinical data and genotype data sharing:
- Re-analysis of DNA samples: N
- Resampling of patients: N
- Linked to a translational/basic research project: N