[Prevalence and geographic distribution of the Wolf-Hirschhorn syndrome in Spain.].

Objective: Wolf-Hirschhorn syndrome is a rare disease of genetic origin caused by the deletion of the distal end of chromosome 4, including at least the region p16.3. The objectives of this work were to determine the prevalence of the disease in the Spanish population, as well as to establish the geographical distribution of the syndrome throughout the Spanish geography, elucidating the age range in which there are more patients.

Methods: Patients diagnosed with the disease for nine years (2013-2021) throughout the Spanish territory were recruited for the research, thanks to agreements with the Spanish Association of Wolf-Hirschhorn Syndrome (AESWH). The clinical information of the patients was obtained from referring physicians using two standardized questionnaires completed with data from medical reports and the parent interview. The molecular characterization of the disease was made using SNP (single nucleotide polymorphism) microarrays (cytoSNP850K, Illumina, USA). The data were statistically processed using Microsoft Excel (Microsoft Corporation) and SPSS (IBM) software, using comparisons between two groups s with Student's t-test (for continuous variables) or with Chi-square tests (for categorical ones). For more than two groups, ANOVA analyses were performed (followed by Bonferroni or T3-Dunnett post hoc tests) for continuous variables and z-tests between column proportions for categorical variables.

Results: In Spain (until 2021) eighty people are diagnosed with this syndrome, estimating its prevalence at 1.69x10-4 per 10,000 inhabitants and / or 1/172,904 for each live newborn. This paper remarks the existence of important differences in prevalence between the different regions in Spain. The region with the most diagnosed patients was Madrid, although the highest prevalence was observed in Asturias. Significant differences have been established in terms of sex and disease (ratio of women to men of 2:1), and the mean age at diagnosis has been established at 7.20 years.

Conclusions: The prevalence of this syndrome in Spain has been estimated well below the prevalence that is handled in scientific texts (1/50,000 newborns). In addition, we have determined that this prevalence shows large geographical differences, which allows us to affirm that this syndrome could be under-diagnosed in our country. Most of the patients included in this cohort are of paediatric age. It has not been possible to corroborate that mortality in this syndrome, in our population, occurs preferably during the first two years of life, as has been claimed.