The neurologic form of neonatal myxedema is characterized by varying degrees of deaf-mutism or lesser degrees of hearing loss, dysarthria, proximal limb and truncal rigid-spastic motor disorder involving mainly the lower extremities, and cognitive impairment of a characteristic type. In the most severely affected, there is also strabismus, kyphoscoliosis, underdevelopment of leg muscles, and frontal lobe release signs. Bone age, head size, and height are normal and there are none of the coarse facial features of the myxedematous form. In the myxedematous form of endemic cretinism, short stature, microcephaly, coarse facial features, and delayed psychomotor development are the main features. There is no deafness or spastic rigidity of the limbs. In typical instances, the face is pale and puffy; the skin dry; the hair coarse, scanty, and dry; the eyelids thickened; the thickened lips parted by the enlarged tongue; the forehead low; and the base of the nose broad. There are fat pads above the clavicles and in the axillae. The abdomen is protuberant, often with an umbilical hernia, and the head is small.
DeLong and others attribute neurologic cretinism to a lack of available iodine in the mother and fetus during the second and third trimesters of pregnancy; neither mother nor fetus produces thyroxine. It is during the latter part of the second trimester, when the cochleas and the neuronal population of the cerebral cortex and basal ganglia are forming, that these structures suffer irreparable damage from lack of thyroid hormone. The effects of this midfetal hypothyroidism and iodine deficiency cannot be corrected by giving thyroid hormone at birth and thereafter. It can be prevented only by providing iodine therapy to the mother before and during the first trimester of pregnancy (Cao et al). The myxedematous form of cretinism is more likely to occur from lack of thyroid hormone in the late second and the third trimesters.
The congenital mental disorder ranges from apathy and absence of social interaction to an alert, cooperative state but slowness in higher-order thinking and verbal facility is always evident. The status of the thyroid gland varies; among patients with the neurologic features of cretinism, about half have goiters or have palpable glands; in the rest, the glands are atrophied; practically all patients with myxedematous cretinism are athyrotic. Although typical examples of neurologic and myxedematous hypothyroidism are readily distinguished, both types may exist in the same endemic area, and stigmata of both forms may be recognized in the same individual. The QRS complex of the ECG is of low voltage; the EEG is slower than normal, with less alpha activity; the CSF contains an excess of protein (50 to 150 mg/dL); and the serum T3 and T4, protein-bound iodine, and radioactive iodine uptake are all subnormal. Serum cholesterol is increased (300 to 600 mg/dL).
At autopsy the brain of neurologic cretinism, although small, is normally formed, with all central and brainstem structures and cortical sulcation intact. A reduction in number of nerve cells was described by Marinesco, especially in the fifth cortical layer, but others have not confirmed this finding. The use of Golgi and other silver techniques has shown decreased interneuronal distances (packing density is increased, as in the immature cortex) where there is a deficiency of neuropil. The latter change is because of a poverty of dendritic branchings and crossings, and presumably there is a decrease of the synaptic surfaces of cells (Eayrs). Thyroid hormone appears to be essential, not for neuronal formation and migration but for dendritic–axonal development and organization.