RESUMO
Nucleotide excision repair associated diseases comprise overlapping phenotypes and a wide range of outcomes. The early stages still remain under-investigated and underdiagnosed, even although an early recognition of the first symptoms is of utmost importance for appropriate care and genetic counseling. We systematically collected clinical and molecular data from the literature and from newly diagnosed NER patients with neurological impairment, presenting clinical symptoms before the age of 12 months, including foetal cases. One hundred and eighty-five patients were included, 13 with specific symptoms during foetal life. Arthrogryposis, microcephaly, cataracts, and skin anomalies are the most frequently reported signs in early subtypes. Non ERCC6/CSB or ERCC8/CSA genes are overrepresented compared to later onset cohorts: 19% patients of this cohort presented variants in ERCC1, ERCC2/XPD, ERCC3/XPB or ERCC5/XPG. ERCC5/XPG is even the most frequently involved gene in foetal cases (10/13 cases, [4/7 families]). In this cohort, the mutated gene, the age of onset, the type of disease, severe global developmental delay, IUGR and skin anomalies were associated with earlier death. This large survey focuses on specific symptoms that should attract the attention of clinicians towards early-onset NER diagnosis in foetal and neonatal period, without waiting for the completeness of classical criteria.
