MON-265 Congenital Hypothyroidism and Bilateral Ptosis Due to a Novel TSHR Gene Mutation

Background. Congenital hypothyroidism (CH) is most frequently caused by thyroid dysgenesis. Approximately 2% of cases with thyroid dysgenesis are familial. TSH receptor (TSHR) gene mutations have been reported in patients with thyroid gland dysgenesis; however, they are not known to be associated with extra-thyroidal anomalies. Clinical case. H.A presented to our clinic at 7 years of age with history of congenital hypothyroidism diagnosed at another institution and started on thyroxine during her first few days of life. Her newborn screen collected on DOL2 showed high TSH of 448 uIU/ml (nl., < 28.5 uIU/ml ) and low T4 of 2.3 ug/dl (nl., > 6.0 ). At age 7 years, her physical exam revealed the absence of a goiter and the presence of mild bilateral ptosis. One year later, a thyroid ultrasound was obtained and it demonstrated a small thyroid gland (right lobe,1.3x0.9x0.3 cm; left lobe, 1.1x1.0x0.2cm ). Her family history was significant for 2 out of her 5 siblings having a history of congenital hypothyroidism, mild ptosis and a small thyroid gland on thyroid ultrasound. Microarray analysis showed several regions of homozygosity including 14q24.2q31.3; of note, the TSHR gene is located in this chromosomal region. Targeted sequence analysis demonstrated a novel homozygous mutation in exon 9 of the TSHR gene (nucleotide change, c.847T>C), which resulted in amino acid change p.C283R. Conclusion. This is the first report of a patient with congenital hypothyroidism and bilateral ptosis due to a novel TSHR gene mutation. The mechanism underlying this association is unknown at this time. Targeted sequence analysis of TSHR gene of her parents as well as her siblings with the same phenotype will be pursued to confirm familial inheritance of this mutation.