Congenital hypothyroidism results in inadequate thyroid hormone production in newborn infants. The cause of this disease in 80 to 85% of cases is due either to the absence, abnormal location or reduced size of the thyroid gland. In the remaining few cases, decreased production of the hormone from a normal thyroid gland causes the disease. Infants that are hypothyroidic show the following symptoms: puffy appearing face, dull look, dry and brittle hair, large tongue protruding from the mouth, sluggishness, lack of interest in nursing, excessive sleepiness, early and prolonged jaundice, difficult respirations and apnea spells, and constipation. Often, there is an involvement of umbilical hernia. The most serious effect of untreated congenital hypothyroidism is mental retardation. Absolute arrest of linear growth and bone maturation may also occur. If left untreated, neurological complications, such as spasticity and gait abnormalities, dysarthria or mutism, and autistic behavior may develop.
Incidence of congenital hypothyroidism ranges between 1 in 3,500-4,000 live births. Diadnosis is made through newborn screening, which analyzes thyroid stimulating hormone (TSH) and/or thyroxine (T4) levels. Replacement therapy with thyroxine is the standard treatment. Prognosis for the patients is very good, if the disorder is detected within the first few weeks.
There are several genes responsible for congenital hypothyroidism. Mutations in the Paired Box Gene 8 (PAX8) and the Thyroid-Stimulating Hormone Receptor (TSHR) gene cause the disease by preventing the development of the thyroid gland. On the other hand, genes like Dual Oxidase 2 (DUOX2), Solute Carrier Family 5 (SLC5A5), Thyroglobulin (TG), Thyroid Peroxidase (TPO), and Thyroid-Stimulating Hormone, Beta Chain (TSHB) play important roles in the production of the thyroid hormone.
Al Shaikh et al. (2003) conducted a retrospective hospital-based study on children with congenital hypothyroidism in Oman. The study group included all children with congenital hypothyroidism who were seen in the endocrine clinic of Royal hospital. These children were further subdivided into two groups: those who were diagnosed by neonatal screening were labeled as group A, while group B were those who were suspected clinically and diagnosed with serum thyroid function test (free T4 and TSH concentrations). Collected data included age at diagnosis, sex, region, cord blood TSH, serum thyroid function test, results of technetium scan and results of IQ assessment (done at school entry age). The total number of children was 45, with 15 males (33%) and 30 females (67%), and this was further divided into group A which included 14 children (31%) with a mean age at diagnosis of 2.3 months, while group B included 31 children (69%) with significantly higher mean age at diagnosis of 9.8 months. The technetium scan on 31 children (71%) revealed higher prevalence of thyroid agenesis (seen in 15 children, 12 from group B and three from group A), while nine children (28%) had ectopic thyroid and eight had dyshormonogenesis (25%). IQ assessment done on 38 patients (84%) revealed that the number of children with normal IQ from group A (67%) were significantly higher than those from group B (15%). Additionally, none of the children from group A had severe mental retardation when compared to 39% from group B who did. In addition, 23% patients from group B had moderate mental retardation as compared to 8% from group A. When comparing the etiology of hypothyroidism with the intellectual outcome, mental subnormality was seen in 8 patients (73%; all from group B) with agenesis of the thyroid, in four (50%) with dyshormonogenesis and in only one (20%) with ectopic thyroid gland. Al-Shaikh et al. (2003) concluded that their study had proved that a large number of children with congenital hypothyroidism were missed or diagnosed late which had caused deterioration in their intellectual function and such complication could be prevented by starting a national screening program for congenital hypothyroidism.
Laditan et al. (1993) reported a case of a 9-year-old Saudi boy, suffering from developmental defects and severe constipation. His parents were consanguineous and none of his family members, including his eight siblings were affected. The patient had no neonatal jaundice, or difficulty in breathing, though he slept excessively. His developmental milestones were delayed, and physically and mentally, he was below average (weight- 3SD below mean; height- 3.5% of mean height for age, IQ- 75). Upon examination, his abdomen was protuberant, liver enlarged, and spleen not palpable. Analysis of the blood showed abnormal values for TSH, FT3, and FT4. X-ray for the hand showed bone age of 1-year, indicating that the hypothyroid state had been of long standing duration. An ectopic sublingual thyroid gland was visualized by Tc-99m thyroid scan. Treatment with sodium L-thyroxine improved the muscular condition, even though the IQ remained the same. One year after therapy, EMG of the patient showed normal study, while muscle biopsy showed signs of muscular dystrophy. Laditan et al. (1993) were of the opinion that earlier diagnosis of hypothyroidism and treatment would have prevented the development of Kocher-Debre-Semelaigne syndrome, and normalized the physical and mental development of the patient.
[Laditan AAO, al-Naim SA, al-Saeed JM, al-Herbish ASA. Congenital hyperthyroidism and muscular dystrophy: Kocher-Debre-Semelaigne syndrome. Case report and review of literature. Emirates Med J. 1993; 11:207-10.]