Alternative titles; symbols
SNOMEDCT: 75065003; ICD10CM: E00.1; ORPHA: 1910;
The clinical manifestations of mental retardation, spastic diplegia, and congenital deafness in various degrees are known as the neurologic type of endemic cretinism, which occurs in countries with high goiter endemicity. Maternal iodine deficiency has been established as a major cause. On the basis of studies of 70 families with endemic cretinism from Highland Ecuador, Held et al. (1990) suggested that an autosomal recessive predisposition is a major etiologic factor. A segregation analysis of 49 families yielded an estimate of P = 0.245. Half sibs were all unaffected and no significant birth order effect was observed among 101 probands. Because the neurologic type of endemic cretinism represents a defined subset of the iodine deficiency disorders, Held et al. (1990) suggested the designation fetal iodine deficiency disorder (FIDD) rather than cretinism.
FIDD is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However, not everyone at risk develops FIDD and familial aggregation is common, suggesting that genetic factors may be involved. The apolipoprotein E (APOE; 107741) gene encodes a lipoprotein that possesses a thyroid hormone-binding domain, and the APOE genotype might affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. In each of 3 iodine-deficient areas in central China, Wang et al. (2000) found that APOE4 genotypes were significantly enriched in FIDD probands, being 16% versus 6% in controls. They suggested that this may contribute to the low frequency of the APOE4 gene in Chinese compared with Caucasian populations.
Held, K. R., Cruz, M. E., Moncayo, F. Clinical pattern and the genetics of the fetal iodine deficiency disorder (endemic cretinism): results of a field study in Highland Ecuador. Am. J. Med. Genet. 35: 85-90, 1990. [PubMed: 2301474] [Full Text: https://doi.org/10.1002/ajmg.1320350116]
Wang, H. Y., Zhang, F. C., Gao, J. J., Fan, J. B., Liu, P., Zheng, Z. J., Xi, H., Sun, Y., Gao, X. C., Huang, T. Z., Ke, Z. J., Guo, G. R., Feng, G. Y., Breen, G, St. Clair, D., He, L. Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China. Molec. Psychiat. 5: 363-368, 2000. [PubMed: 10889546] [Full Text: https://doi.org/10.1038/sj.mp.4000735]