IMPE Abstracts

Background: Simpson Golabi Behmel syndrome (SGBS) is caused by loss-of-function mutations in the GPC3 gene, which encodes glypican-3, a cell-surface heparan sulfate proteoglycan that acts as a negative regulator of the Hedgehog signaling pathway during development. GPC3 mutations result in hyperactivation of Hedgehog signaling ultimately leading to pre- and postnatal overgrowth and cancer. On the other hand, thyroglossal duct cyst (TGD) is a common congenital anomaly in the midline of the neck, although, thyroglossal duct cyst carcinomas (TGDC) are rare in the pediatric population, with less than 60 cases reported to date. We describe a new mutation of the GPC3 gene in a patient with SGBS who presented papillary thyroid cancer (PTC) in TGDC.

Case presentation: A 9-year-old male patient with a history of tall stature, macrocephaly, dysmorphic features, and neurodevelopmental delay since 2 years of age. As relevant history, he was born prematurely at 32 weeks with a birth weight of +1.82SD and height of +1.9SD (INTERGROWTH-21st). At 6 years old, I have presented a mass in the anterior triangle of the neck compatible with a TGD which was resected. Pathology reported commitment by a non-encapsulated follicular variant of PTC in the cyst. Total thyroidectomy with central lymph node dissection was indicated. The pathology was negative for malignancy. Three years later he was admitted to emergency with a myxedema coma, apparently with poor adherence to treatment with levothyroxine. Tests reported high thyroid-stimulating hormone, suppressed free thyroxine and rising thyroglobulin. Iodine-131 whole-body scan showed a possible recurrent lesion. Magnetic resonance imaging of the neck showed pseudocysts lesion at the base of the tongue compatible with acquired ranula, lymph nodes not suspicious for malignancy, and he was discharged. An exome requested as part of the overgrowth syndrome study reported probable pathogenic variant c.1090G>T;p. (Glu364*), in hemizygous, in GPC3 gene compatible with the genetic diagnosis of SGBS type 1, with X-linked recessive inheritance.

Conclusions: In our case, it is possible that the presence of a mutation in the GPC3 gene has predisposed a congenital anomaly such as TGD. However, despite people affected by SGBS are at increased risk of cancer, to date, there is no data linking SGBS with thyroid cancer. It is not clear, whether the presence of a mutation in the GPC3 gene in our patient confers a higher risk of recurrence and distant metastasis.