Endocrine Abstracts

Introduction: Congenital hypothyroidism (CH) is the most common congenital endocrine disease since it affects 1/3000–1/4000 births. The involvement of genetics is no longer discussed and several genes have been implied in the different clinical forms of thyroid dysgenesis.

Patients and methods: We report ten cases of thyroid dysgenesis collected at the pediatric and endocrinology departments of Sfax in Tunisia. The diagnosis was based on clinical, biological, morphological investigations of the thyroid gland. To investigate genetic abnormalities involved in the onset of CH in Tunisian families, first, we investigated the case of non-syndromic CH, by looking for mutations in the TSHR gene. Then we look for correlation genotype – phenotype for this gene and other genes involved thyroid development.

Results: Our study consisted of six girls and four boys of 22 months average age at the time of diagnosis. Parental consanguinity was noted in 80%. Three cases of familial form were recored with an autosomal recessive mode of transmission for two and autosomal dominant for the remaining case. The signs of dysthyroidism and delayed stature were the main circumstances of discovery. The non-syndromic form was the most common form. The syndromic associations noticed in the remaining cases were renal impairment, facial dysmorphism. Biologically, thyroid status confirmed peripheral hypothyroidism in all cases. At the end of this assessment, five of our patients had hypoplasia suggestive of TSH resistance syndrome. A mutation of the TSHR is evoked for four4 of these patients. However the molecular analysis TSHR revealed a known polymorphism (c.561T> C (rs 2075179) in exon 7 of the TSHR gene in a homozygous state in a patient with CH and in a heterozygous state in a another patient. No mutation was revealed at that time and the study of other exons is still being analyzed. For the remaining case, resistance to TSH due to Gs protein deficiency was strongly suspected in the presence of pseudohyperparathyroidism. For the three cases of ectopia, the NKx2-5 and TTF-2 genes can be incriminated. A mutation of the PAX8 gene is strongly suspected in association with a renal anomaly in one case. For the facial dysmorphism noticed in one case, we will complete with FISH study in search of microdeletion7q11.23.

Conclusion: In this work, we have illustrated the contribution of molecular diagnosis of thyroid dysgenesis to establish adequate genetic counseling for families at risk in the lack of systematic neonatal screening.