Thyroid Hypoplasia as a Cause of Congenital Hypothyroidism in Monozygotic Twins Concordant for Rubinstein-Taybi Syndrome

Abstract

Rubinstein-Taybi syndrome (RSTS), a genetic disorder characterized by growth retardation, mental deficiency, dysmorphic face, broad thumbs and large toes, generally affects monozygotic twins concordantly. Thyroid hypoplasia (TH) is a common cause of congenital hypothyroidism (CH) and often accompanies dysmorphic syndromes. A pair of female twins were admitted to our neonatology unit 16 hours after delivery. They were born at 35 weeks of gestation. Both twins had an unusual dysmorphic facial appearance with microcephaly, as well as broad short thumbs and large toes. Based on the presence of characteristic dysmorphic features, the twins were diagnosed as RSTS. Thyroid function tests in the first twin revealed the following results: free thyroxine (T4) 8.4 pg/mL, thyrotropin (TSH) 4.62 mIU/L, thyroglobulin (TG) 213.24 ng/mL and a normal level of urinary iodine excretion (UIE). Thyroid function test results in the second twin in the second week were: free T4 5.9 pg/mL, TSH 9.02 mIU/L, TG 204.87 ng/mL, and normal UIE levels. Thyroid volumes were 0.36 mL and 0.31 mL in the first and second twin, respectively. TH was confirmed by technetium 99 m pertechnetate thyroid scans in both infants. Thyroid function tests normalized with L-thyroxine replacement therapy (10 μg/kg/day) around the end of the 3rd week of life. The infants were discharged planning their follow-up by both endocrinology and cardiology units. The rarity of cases of twins with RSTS (concordant) co-existing with CH led us to present this report. Conflict of interest:None declared.

Rubinstein-taybi syndrome: Clinical profile of 11 patients and review of literature

“…Most cases of RSTS are sporadic, and families with more than 1 affected child are extremely rare. [ 20 ] The known genetic causes of RSTS are point mutations or microdeletions of CREB-binding protein gene (CREBBP) located on chromosome 16p 13.3 (in 50-60% affected patients), and of the EP300 gene encoding E1A binding protein p300 localized on 22q13.2 (in 5% patients). [ 6 8 21 ] The mutations causing RSTS are almost always de novo occurring in autosomal dominant fashion.…”