Study of the pathophysiological mechanisms associated with the onset and course of neurodevelopmental disorders in preterm infants (the PeriSTRESS-PremTEA study): Rationale, objectives, design and sample description. / Estudio de los mecanismos fisiopatológicos asociados al inicio y curso de los trastornos del neurodesarrollo en prematuros (estudio PeriSTRESS-PremTEA): justificación, objetivos, diseño y descripción de la muestra.

BACKGROUND: There are few studies exploring the pathophysiological pathways that may condition differentially the emergence/course of neurodevelopmental disorders (ND) in very preterm and extremely preterm newborns (VPTN/EPTN). Furthermore, there are no established biological markers predictive of ND in this population. The aim of this study is four-fold: in two cohorts of VPTN/EPTN (i) to characterize the emergence/course of ND up to corrected-age 6 years, (ii) to identify those factors (from prenatal stages up to age 6 years) that explain the interindividual differences related to emergence/course of ND, (iii) to identify in the first hours/days of life a urinary metabolomic biomarker profile predictive of ND, and (iv) to determine longitudinally variations in DNA methylation patterns predictive of ND. METHODS: Observational, longitudinal, prospective, six-year follow-up, multicentre collaborative study. Two cohorts are being recruited: the PeriSTRESS-Valencia-cohort (n=26 VPTN, 18 EPTN, and 122 born-at-term controls), and the PremTEA-Madrid-cohort (n=49 EPTN and n=29 controls). RESULTS: We describe the rationale, objectives and design of the PeriSTRESS-PremTEA project and show a description at birth of the recruited samples. CONCLUSIONS: The PeriSTRESS-PremTEA project could help improve early identification of clinical, environmental and biological variables involved in the physiopathology of ND in VPTN/EPTN. It could also help to improve the early identification of non-invasive ND biomarkers in this population. This may allow early ND detection as well as early and personalised intervention for these children.

Phenotypic variability in a four generation family with a p.Thr666Met CACNA1A gene mutation.

BACKGROUND: Familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6 are distinct neurological disorders associated with mutations in the CACNA1A gene. Phenotypic variability and clinical overlap are recognized. PATIENTS: We describe a 2-year-old child with transiently decreased consciousness and clinical and radiological signs of early-onset cerebellar atrophy. The family history was significant, and 11 affected members across four generations indicated an unusually wide clinical spectrum including migraine, hemiplegia, coma, and progressive cerebellar ataxia. RESULTS: The p.Thr666Met mutation of the CACNA1A gene was identified in the index patient and in five of his affected relatives who were analyzed. Our patient is the youngest one of this entity diagnosed to date. CONCLUSIONS: Taking into account such a wide clinical expression of these gene mutations, it could be more accurate to speak about "channel-related diseases" to characterize the clinical expression according to the genetic analysis and to the phenotypes associated with each CACNA1A gene mutation.