THE EFFECT OF MENDELIAN DISEASE ON HUMAN HEALTH - A MEASUREMENT

An attempt to measure effects of Mendelian phenotypes on human health (homesotasis) in man is described. The McKusick Catalogs were used as the source for descriptions of autosomal dominant, recessive and X-linked phenotypes. Entries (351) (76% of the initial sample) were disadaptive causing an impairment, disability, or handicap. (Terms used are in accordance with WHO definitions.) Phenotypic effects were scored to measure impact on life-span, reproductive capability and psychosocial characteristics. Of the disadaptive Mendelian phenotypes, 25% were apparent at birth and over 90% by the end of puberty; age at onset is unimodal in distribution for autosomal recessive and X-linked diseases and trimodal for autosomal dominant (with modes during morphogenesis, infancy and early adult life); 58% of phenotypes involved > 1 anatomical or functional system; autosomal dominants were more likely to involve only a single system; life-span was reduced in 57%, particularly in those with onset in pre- or intra-reproductive life and more often in recessive and X-linked diseases (data corrected for genetic lethals); prognosis varied with system involvement; reproductive capability was impaired in 69% of phenotypes; and most phenotypes compatible with life beyond infancy caused psychosocial handicap and limited the access to schooling and work. These findings have implications for medical care.