ESPE Abstracts

Background: Tuberous sclerosis (TS) is a polymorphic, dominantly inherited syndrome caused by an inactivating mutation in tumor suppressor genes, TSC1 or TSC2; they regulate mammalian target of rapamycin (mTOR), a key player in control of cellular growth and protein synthesis. The disease involves benign tumors in several distinct organs (such as the skin, kidneys, heart, and CNS), that can interfere with organ function. Rarely TS is associated with endocrine abnormalities, and almost never witn congenital hypothyroidism.

Objective and hypotheses: EG was a female newborn, positive at neonatal screening for congenital hypothyroidism (CH) (confirmed with venous sample). USgraphy and scintigraphy showed hypo-dysplasia of her thyroid (treated with L-tiroxine). As a part of diagnostic approach, we made echocardiography, founding several rabdomiomas. These benign tumors are frequently associated with TS, so we searched for mutations of TSC1 and TSC2 genes. EG had also brain nuclear magnetic resonance (NMR) and abdominal organs echographies (normal). No skin lesions were found.

Method: DHPLC and polimorfisms sequencing of TSC1 and TSC2 genes.

Results: EG had heterozygosis in pLeu697Ser^ of TSC2 exon 18 and p.Asn762Ser mutation of TSC1 exon 18. The same abnormalities were found in her father. The brain NMR showed a small altered signal in left front-insular white substance. EG had later seizures, so she had to begin therapy with valproic acid.

Conclusion: Although the association of CH and TS in one patient may be merely coincidence, we speculate that the dysgenetic thyroid gland in this baby can be a ‘hamartia’ as a consequence of the tuberous sclerosis gene mutation.