CLUSTERING OF CONGENITAL ATHYREOTIC CRETINISM

Abstract

Congenital athyreotic cretinism (CAC) occurs in more than one sibling or relative on rare occasion. Heterogeneity with the existence of an autosomal recessive form has been evoked as the most plausible explanation, yet almost all cases occur sporatically without apparent cause. The Kentucky experience has been different in that a disproportionate number of CAC cases have come from the same rural community with two sets of affected siblings as first cousins.

Since 1963 we have cared for 25 infants and children (13M, 12F) with CAC, and most have come from distant communities. Six have been clustered in South Madison County, four being two sets of affected siblings who are first cousins. In addition, three older sibs of this kindred died in infancy and childhood with histories and photographs suggestive of CAC. All the Madison County families live within ten miles of each other, and all have lived in the community for generations. Additionally, two brothers with CAC have come from another county. There is no apparent consanguinity in any of the families, and identification of cretins in earlier generations is unreliable. The population is stable, homogenous and of English origin. Other thyroid disease occurred in second degree relatives in six families.

Geographic clustering and familial aggregation of CAC in rural communities with sparse population suggest a common pathogenic mechanism leading to failure of embryonic thyroid development. A Mendelian trait for the defect which is enhanced by additional genetic influences is the best explanation.

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