Resistance to thyroid hormone due to mutations inactivating thyroid hormone receptor-Beta occurs in one in 40,000 individuals and can arise de novo or be inherited, generally in a dominant fashion. Clinical manifestations are widely variable and include failure to thrive in infancy. The biochemical diagnosis is usually straightforward: high serum fT4 and non-suppressed TSH.
We report two brothers who both inherited the known c.728G>A, p.R243Q mutation in TRHB from their mother, who had been diagnosed at age 20 in the course of blood work for fatigue: fT4 31 pmol/L, TSH 2.8 mU/L. Both pregnancies were uneventful, except for the ultrasound finding in sibling # 2 that the right kidney was small and contained multiple cysts. As there was no indication of fetal hyperthyroidism, no prenatal diagnosis was attempted. Both were born at 37 weeks, with birth weights of 2926g for sibling #1 and 2920g for sibling #2. Sib # 2 had a preauricular tag. Both sibs had inherited the maternal mutation. There was neither sign of thyroid dysfunction nor goiter. On day 2, blood spot TSH was 1.4 and 5.2 mU/L; serum TSH was 3.28 and 4.26; fT4 39.6 and 53.37, respectively. Both were discharged on day 2 and exclusively breastfed. However, sibling # 2 was admitted on day 5 for stridor. Laryngomalacia was diagnosed. On day 10, a CT angiogram was performed and did not show any malformation of the heart or vessels. At 2 months, the association of failure to thrive (weight 3 SD) with laryngomalacia and abnormal right kidney development led to the diagnosis of Di George syndrome (22q.11 deletion). This deletion was absent in the parents. Feeding with an enriched formula led to catch-up growth.
To our knowledge, sibling # 2 is the first reported case of simultaneous RTH and 22q11 deletion. While there is no obvious biological link between the two conditions, it is the contrast with the postnatal evolution of sibling # 1 that led us to broaden the diagnostic investigations in sibling # 2.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology