The syndrome of anosmia with hypogonadotropic hypogonadism: A genetic study of 18 new families and a review

Authors

  • Dr. Beverly J. White,

    Corresponding author
    1. Section on Cytogenetics, National Institutes of Health, Bethesda, Maryland
    2. Digestive and Kidney Diseases, Inter-Institute Genetics Clinic, National Institutes of Health, Bethesda, Maryland
    • Room 4D-48, Building 10, National Institutes of Health, Bethesda, MD 20205
    Search for more papers by this author
  • Dr. Alan D. Rogol,

    1. Clinical Endocrinology Branch, National Institute of Arthritis, Diabetes, National Institutes of Health, Bethesda, Maryland
    Current affiliation:
    1. Department of Pediatrics and Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908
    Search for more papers by this author
  • Kenneth S. Brown,

    1. Digestive and Kidney Diseases, Inter-Institute Genetics Clinic, National Institutes of Health, Bethesda, Maryland
    2. Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • Dr. Jeffrey M. Lieblich,

    1. Clinical Endocrinology Branch, National Institute of Arthritis, Diabetes, National Institutes of Health, Bethesda, Maryland
    Current affiliation:
    1. Department of Medicine, Highland Park Hospital, Highland Park, IL 60035
    Search for more papers by this author
  • Saul W. Rosen,

    1. Clinical Endocrinology Branch, National Institute of Arthritis, Diabetes, National Institutes of Health, Bethesda, Maryland
    Search for more papers by this author
  • John M. Opitz

    EditorSearch for more papers by this author

Abstract

Among 18 NIH probands with anosmia and hypogonadotropic hypogonadism (AHH), seven had affected relatives and three had consanguineous parents. Both sexes were equally affected and parents were phenotypically normal. Parental age was not increased. Cleft lip and palate occurred in both eugonadal and hypogonadal persons, a previously reported association that may represent variable expression of AHH. Diabetes mellitus, usually insulin-dependent, was frequent in probands and their families. Other common traits included obesity, cryptorchidism, and hearing loss. All probands were chromosomally normal. The frequency of some dermatoglyphic traits of probands differed from normal, but no trait was unique to AHH.

Segregation analysis of our proband sibships was consistent with a hypothesis of autosomal-recessive inheritance with variable expression. However, genetic heterogenety was apparent when previous reports of familial AHH were surveyed. An X-linked or male sex-limited autosomal-dominant form with unilateral renal agenesis, mental retardation, and hypotelorism has been observed. The infrequent reports of direct male-to-male transmissionn limit characterization of an autosomal-dominant form of AHH.

Our phenotypic analysis suggests that the traits of mental retardation, renal anomalies, hypotelorism, diabetes, and hearing loss may help to distinguish various forms of AHH, whereas cryptorchidism, clefts, and obesity appear in several types of families. At present, genetic counseling is dependent upon establishing inheritance pattern after examination for the known associated anomalies.

Ancillary