Abstract:
Introduction: Hypospadias, a complex urogenital malformation, raises significant
concerns in pediatric urology due to its varied clinical implications. This thesis focused on
a comprehensive approach, including an epidemiological study and a molecular analysis,
aimed at elucidating the risk factors and genetic bases of this condition within the Algerian
population.
Methods: A retrospective epidemiological study was conducted on cases operated on
between 2007 and 2022 in eastern Algeria. Molecular analysis was performed on 110
patients and 125 controls using PCR and PCR/RFLP techniques to examine genetic
variations.
Results: The retrospective epidemiological study revealed a stable prevalence of
hypospadias, with the majority of cases managed between 0 and 5 years. Duckett's
classification highlighted a predominance of cases with an anterior urethral meatus
position, while severity assessment showed that approximately a quarter of the cases were
severe, often associated with complex genital anomalies such as micropenis and testicular
ectopia. Risk factor analysis highlighted significant associations with advanced maternal
age, diabetes, and gestational hypertension, as well as consanguinity. Neonatal parameters
like low birth weight and prematurity were also strongly correlated with this malformation.
The molecular analysis enhanced our understanding of the genetic bases of hypospadias in
the Algerian population. Y chromosome microdeletions were absent in all studied patients.
Conversely, significant associations were found between the C677T variant of the MTHFR
gene and the risk of hypospadias, suggesting that hyperhomocysteinemia related to this
variant might disrupt folate metabolism and affect embryonic genital development. In
contrast, analysis of the A>G variant of the DICER1 gene did not reveal a correlation with
hypospadias, although the G allele is rare in this population.
Conclusion: This thesis makes significant contributions to the integrated understanding of
epidemiological and genetic factors of hypospadias in Algeria. The results highlight the
importance of a multidisciplinary approach for clinical management and future research,
aiming to improve early screening, surgical management, and preventive strategies for this
complex medical condition.