Targeted genes under study:
PLK4, TUBGCP4, TUBGCP6, RBBP8, KIF14, KIF11
Primary Microcephalies (PMs) are characterized by a reduction in brain size, associated or not with a reduction in body size, mainly with a recessively inheritance. To date, mutations in more than 50 genes have been identified as responsible for PMs, now including microcephaly primary hereditary (MCPH 1-30), and microcephalic dwarfisms. The neurological phenotypes associated with mutations in each of these genes are being refined as publications progress, including cortical malformations or neurosensory disorders. However, developmental and cognitive consequences of such a reduction in brain volume that can reach 50% are still unknown as very few patients (<5%) have undergone a neuropsychological evaluation.
This is particularly true for PMs with neurosensory impairment, caused by mutations in PLK4, TUBGCP6, TUBGCP4, KIF14, and RBBP8 which are even rarer (respectively reported in only 15, 14, 5, 16, and 2 patients). Even if the dominant form of PM caused by mutations in KIF11 gene is more frequent and extensively studied regarding the ophthalmological features (chorioretinopathy, exudative vitreoretinopathy reported in 58 patients), none of these patients have performed neuropsychological tests.
To define their cognitive abilities, and establish whether correlations between their cognitive abilities and their head circumference or their genotype exist, we would like to collect data of patients carrying mutations in one of the genes listed below, including growth parameters, brain MRI and motor, language, and cognitive development assessed by international neuropsychological tests.
We also aim to describe the ophthalmological features of the rarer forms.
We would like to add these data to those of the 10 patients already included into the medical thesis of Mathilde Gras.
This work will lead to a better understanding of the intellectual abilities of these patients to precise their autonomy in adulthood and to deliver a more precise genetic counselling to parents when detected prior birth.
Hôpital Robert Debré, Université Paris Cité, Paris, France
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: No
3- Linked to a translational/basic research project: No