Journal of Clinical Endocrinology & Metabolism, Vol 78, 1525-1528, Copyright © 1994 by Endocrine Society

ARTICLES

Low intelligence but not attention deficit hyperactivity disorder is associated with resistance to thyroid hormone caused by mutation R316H in the thyroid hormone receptor beta gene

RE Weiss, MA Stein, SC Duck, B Chyna, W Phillips, T O'Brien, L Gutermuth and S Refetoff
Department of Medicine, University of Chicago, Illinois 60637.

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of tissues to thyroid hormone. The clinical manifestations are variable and 46-50% of children with RTH have attention deficit hyperactivity disorder (ADD). We present a new family with RTH (F120) found to have a mutation R316H in the thyroid hormone receptor beta (TR beta) gene identical for that reported in an unrelated family. Assignment of the mutant allele and haplotyping based on CA repeat polymorphism were done on 16 family members. Semistructured diagnostic interviews and psychometric testing were used to determine the psychiatric diagnosis of 12 family members by examiners blinded to the genotype. Three subjects were identified to have the R316H allele as well as mildly elevated free T4 index (168 +/- 12; normal range 77-135) and nonsuppressed TSH (4.1 +/- 1.7 mU/L). Only 2 of the subjects with RTH were found to have ADD, while one family member homozygous for the wild type TR beta and normal thyroid function tests also had ADD. Unaffected family members had higher full scale intelligence quotients (IQ) (93 +/- 7) than any of the 3 family members with RTH (77 +/- 5, p = 0.006). These data do not support the genetic linkage of ADD and RTH, but do suggest that RTH is associated with lower IQ scores that may confer a high likelihood of exhibiting ADD symptoms.

This article has been cited by other articles:

				D. E. COMINGS Clinical and Molecular Genetics of ADHD and Tourette Syndrome: Two Related Polygenic Disorders Ann. N.Y. Acad. Sci., June 1, 2001; 931(1): 50 - 83. [Abstract] [Full Text] [PDF]

				P. L. PEARL, R. E. WEISS, and M. A. STEIN Medical Mimics: Medical and Neurological Conditions Simulating ADHD Ann. N.Y. Acad. Sci., June 1, 2001; 931(1): 97 - 112. [Abstract] [Full Text] [PDF]

				R. E. Weiss and S. Refetoff Editorial: Treatment of Resistance to Thyroid Hormone--Primum Non Nocere J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 401 - 404. [Full Text]

				M. P. McDonald, R. Wong, G. Goldstein, B. Weintraub, S.-y. Cheng, and J. N. Crawley Hyperactivity and Learning Deficits in Transgenic Mice Bearing a Human Mutant Thyroid Hormone beta 1 Receptor Gene Learn. Mem., September 1, 1998; 5(4): 289 - 301. [Abstract] [Full Text]

				A. T. Dugbartey Neurocognitive Aspects of Hypothyroidism Arch Intern Med, July 13, 1998; 158(13): 1413 - 1418. [Abstract] [Full Text]