OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: PAX8

Nongoitrous congenital hypothyroidism
Thyroid dysgenesis
Kocher-Debre-Semelaigne syndrome

Athyreotic hypothyroidism
Thyroid dysgenesis
Thyroid hypoplasia
Developmental delay
Short stature
Cool, dry, mottled skin
Enlarged tongue
Hoarse voice

Congenital Hypothyroidism

Clinical Characteristics

General description (for patients):

Infants born with low thyroid levels often appear lethargic and rather listless within the first month of life.  If untreated, they are slow in overall development and short in stature.  Their face appears “puffy”, the bridge of the nose is often flattened and they can have a dull, open-mouthed appearance.  The abdomen is protuberant and sometimes the arms and legs appear muscular.  The skin is often cool, dry, and mottled.   The tongue can be enlarged, and the voice may be hoarse.  Developmental milestones like sitting, talking, and walking are delayed.

Medical description:

Low thyroid hormone levels from birth can result from several mechanisms such as a dysplastic or absent thyroid, or lack of thyroid-stimulating hormone (TSH). The dysplastic variety has been reported in two sibs in Holmes County, in which a small amount of thyroid tissue was demonstrated in one by technetium-99M scanning. These sibs also had muscular hypertrophy as sometimes seen in hypothyroidism, a combination in children known as the Kocher-Debre-Semelaigne syndrome. These female sibs were developmentally delayed in all parameters. They had typical signs such as a dull, open-mouthed faces, enlarged tongues, a flat nasal bridge, cool, dry and mottled skin, dry, coarse hair and a protuberant abdomen. Following adequate treatment with levothyroxine, their affect, growth, and activity levels become nearly normal as does their physical appearance.


Congenital hypothyroidism is etiologically heterogeneous disorder. A substantial number of cases seem to be caused by a mutation in the PAX8 gene located on chromosome 2 (2q12-q14).


Early diagnosis is important since administration of levothyroxine can correct virtually all of the signs and symptoms of this disorder while delayed treatment results in permanent mental and growth retardation.


If treated early, prognosis for a normal life is good.

Ancillary treatments and support:

Early initiation of therapy requires little further treatment beyond lifelong thyroid hormone supplementation. Careful follow-up and monitoring is important especially in children to maintain the proper dosage of levothyroxine.

Specialists and specialty centers:

Pediatrician, endocrinologist.


Cross, H.E., Hollander, C.S., Rimoin, D.L., and McKusick, V.A.: Familial agoitrous cretinism accompanied by muscular hypertrophy. Pediatrics 41: 413-420, 1968.  PubMed ID: 5637792

Fisher, D.A.: Second International Conference on neonatal thyroid screening: progress report. J. Pediat. 102: 653-654, 1993.  PubMed ID: 6842320

Castanet, M., Lyonnet, S., Bonaiti-Pellie, C., Polak, M., Czernickow, P., and Leger, J.: Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism (Letter). New Eng. J. Med. 343: 441-442, 2000.  PubMed ID: 10939901


Thyroid Hormone and Disease Information

Endocrine Web

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