Vesicoureteral reflux is now recognized to be hereditary and familial. The incidence of reflux in siblings has proved to be significant but less is known about the incidence of reflux in the offspring of known reflux patients. In an ongoing prospective series of reflux screening we identified 23 patients of childbearing age with a known history of reflux and screened their 36 offspring with an awake voiding cystourethrogram. Of these 36 offspring 24 (66%) exhibited vesicoureteral reflux. The literature was also reviewed to determine the incidence of parent/child reflux from reported cases. This review revealed a 65% rate of reflux in the offspring of known patients. Our preliminary results coupled with those in the literature signify a need to screen the offspring of known reflux patients and suggest a rethinking of the genetic transmission for this trait. While vesicoureteral reflux could still be a multifactorial genetic trait with a major gene, consideration must also be given to an autosomal dominant inheritance pattern.

Hypophosphatasia, a rare heritable form of rickets/osteomalacia, is characterized by deficient activity of the tissue nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequence of either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5 1/2 years and has had a much milder clinical course. Although consanguinity is absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are consistent with heterozygosity in each parent. Fibroblast ALP activity is less than 1% normal in all 3 patients with no complementation observed in heterokaryon analysis. Accordingly, the genetic defects appear to be identical in all 3 patients. Our findings show that infantile hypophosphatasia may be inherited as an AR condition where there is variable expressivity and that homozygosity or compound heterozygosity, as may be the case in this family, is not necessarily lethal.

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