CRETINISM

 Cretinism refers to hypothyroidism that develop in infancy or early childhood. The term cretin was derived from the French chretien ,meaning Christian or Christlike, and was applied to these unfortunates because they were considered to be so mentally retarded as to be incapable of sinning. 

In the Past ,this disorder occurred fairly commonly in areas where dietary iodine deficiency is endemic , such as the Himalayas, inland China , Africa and other mountainous areas. It has become much less frequent in recent years, owing to the widespread supplementation of food and iodine. 

On rare occasions, cretinism may also result from inborn errors in metabolism ( e.g. enzyme deficiencies) that interfere with the biosynthesis of normal levels of thyroid hormone ( sporadic cretinism).

Clinical feature of Cretinism include impaired development of the skeletal system and central nervous system, manifested by severe mental retardation ,short stature , coarse facial features, a protruding tongue, and umbilical hernia.

The severity of the mental impairment in cretinism appears to be related to the time at which thyroid deficiency occurs in utero.

Normally , maternal hormones, including T3 and T4 , cross the placenta and are critical to fetal brain development. If there is maternal thyroid deficiency before the development of the fetal thyroid gland , mental retardation is severe. In contrast , reduction in maternal thyroid hormone later in pregnancy, after the fetal thyroid has developed, allow normal brain development.

Cretinism is primarily caused by genetic mutation that affect the development and functions of the thyroid gland,which is responsible for producing and secreting thyroid hormones. These mutations can affect different genes involved in the synthesis, transport or function of thyroid hormone, leading to a decrease in the production or availability to these hormones.

There are several different genetic cause of Cretinism, including :

1. Thyroid dysgenesis : This refers to a group of genetic disorders that affects the development of thyroid glands, leading to decrease in thyroid hormones. Mutation in genes such as TSHR, PAX8 , NKX2-1, have been associated with thyroid dysgenesis.

2. Thyroid hormone synthesis defects : these are genetic disorders that affect the enzymes involved in the synthesis of thyroid hormones. Mutation in gene such as TPO, DUOX2, and DUOXA2 can lead to a decrease in the production of thyroid hormones.

3. Thyroid hormone trasport defects : These are the genetic order that affect the transport of thyroid hormone in the body. Mutation in gene such as MCT8 and SLC16A2 can lead to a decrease in the availability of thyroid hormones to the develop brain.