HUT (Hutterite)

Inheritance: autosomal recessive
Genes: PROP1

Panhypopituitarism
Ateliotic dwarfism with hypogonadism
Pituitary hormone deficiency combined
CPHD

Growth hormone deficiency
Dwarfism
Hypothyroidism
Hypoadrenalism
Hypogonadism
Hypotiuitarism

Pituitary Dwarfism III

Clinical Characteristics

General description (for patients):  

Failure of the pituitary gland to develop and function normally results in the clinical picture of dwarfism, undeveloped gonads, low thyroid function and a deficiency in adrenal hormones. Lack of growth is usually evident by the age of six years. Puberty does not occur unless sex hormones are supplied. Early recognition is important to normal development for hormonal replacement therapy is highly effective.

Medical description: 

Generalized loss of pituitary function results in a deficiency of growth hormone, ACTH, gonadatropins, and thyroid stimulating hormone with predictable signs and symptoms.  Heritable cases are rare. But sibships with multiple affected individuals consistent with autosomal recessive inheritance have been reported. Onset of symptoms is evident by growth failure midway in the first decade of life. Growth hormone and TSH deficiencies can be demonstrated at that time while sex hormone therapy becomes necessary at puberty.  ACTH deficiency may not be clinically evident until later. The sequential pattern of hormone deficiencies may vary, however. In one Hutterite family three sibs who were not treated showed growth hormone and gonadotropin deficiencies during the first decade, with subsequent loss of TSH function, and did not develop ACTH deficiency until the third decade. In another family, deficiencies of growth hormone, gonadotropins and TSH were all evident in the first decade of life.

Genetics:

Panhypopituitarism can result from autosomal recessive mutations. The Hutterite cases in three families in which all six parents descended from four common ancestral couples have been shown to have a two base pair deletion (301-302delAG) in the PROP1 gene.

Treatment: 

Hormone replacement.

Prognosis:

Highly dependent upon age of diagnosis and success of hormone replacement.

Ancillary treatments and support:

Case-specific dependent on nature of hormonal deficiency.

Specialists and specialty centers:

Endocrinologist, pediatrician.

References:

McArthur, R.G., Morgan, K., Phillips, J.A. (III), Bala, M., and Klassen, J.: The natural history of familial hypopituitarism. Am. J. Med. Genet. 22: 553-566, 1985. PubMed ID: 2998186

Bottner, A., Keller, E., Kratzsch, J., Stobbe, H. Weigel, J.F., Keller, A., Hirsch, W., Kiess, W., Blum, W.F., and Pfaffle, R.W.: PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis. J. Clin. Endocrinol. Metab. 89: 5256-5265, 2004. PubMed ID: 15472232

Wu, W., Cogan, J.D., Pfäffle, R,W,, Dasen, J.S., Frisch, H., O'Connell, S.M., Flynn, S.E., Brown, M., Mullis, P.E., Parks, J.S., Phillips, J.A., 3rd, and Rosenfeld, M.G.:  Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet 18(2):147-149, 1998. PubMed ID: 9462743

Resources:

Little People of America
Pituitary Network Association

Associated Graphics