John C. Gall

Metacarpophalangeal Pattern Profiles in the Evaluation of Skeletal Malformations

Metacarpophalangeal pattern profile analysis is a graphic method of depicting lengthening and shortening of the tubular bones of the hand and their relationship to one another. The lengths of the tubular bones are plotted in terms of standard deviation units. These data are derived from simple measurements from hand radiographs and related to age and sex norms. Comparison of these patterns is a more sensitive index for detecting similarity of hand radiographs than is simple inspection of the radiograph. Since many congenital malformations have characteristic metacarpophalangeal pattern profiles, the method can be useful in the diagnosis and definition of these conditions.

Skeletal manifestations of the Holt-Oram syndrome.

The Holt-Oram syndrome is an autosomal dominant trait consisting of characteristic upper-limb abnormalities and congenital heart disease. Shoulder abnormalities are typical. Carpal abnormalities are distinctive and may be present even when the digits are normal. The most striking carpal abnormality is the presence of extra carpal bones. Carpal anomalies appear to be more specific for Holt-Oram syndrome than thumb changes. Prominent laterally and posteriorly protuberant medial epicondyles of the humeri are seen in many patients. The lower extremities are normal.

The hand-foot-uterus syndrome: A new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract**

A new hereditary syndrome is described in 13 living members of 4 generations in a single kindred. The syndrome is characterized by malformations and hypoplasia of the hands and feet, and by varying degrees of duplication of the female genital tract. Radiographic findings in the hands and feet, and associated dermatoglyphic patterns, are characteristic of the syndrome. It is transmitted as an autosomal dominant with full penetrance and variable expression.

Electrophoretic variation in human serum ceruloplasmin: A new genetic polymorphism

Through the application of a specific oxidase stain to results of starch gel electrophoresis of human serum, three different electrophoretic forms of ceruloplasmin—denoted CpA (fast), CpB (intermediate), and CpC (slow)—have been defined. The electrophoretic differences are small and were first recognized through a rare variant individual who had only the fast and slow forms. Five phenotypes displaying different combinations of the three electrophoretic forms have been defined in American Negroes; these are called CpA, CpAB, CpB, CpAC, and CpBC. Twin, family, and population studies have yielded evidence indicating that the A and B electrophoretic forms are controlled by a pair of autosomal codominant alleles, designated CpAand CpB, and suggesting that the C form may be determined by a third allele, CpC, at the same locus. The variants constitute a genetic polymorphism in American Negroes, but occur only rarely in Caucasians.

Radiographic findings in the hand-foot-uterus syndrome (HFUS).

The hand-foot-uterus syndrome is a hereditary disorder with abnormalities involving the hands and feet. Females with the disorder have duplications of the genital tract. Radiologically, the metacarpals and metatarsals are shortened and unusual carpal and tarsal fusions are present. Clinodactyly of the fifth fingers and short, pointed distal phalanges of the thumb and great toe are apparent.

Inheritance of quantitative expression of erythrocyte glucose-6-phosphate dehydrogenase activity in the Negro—a twin study

Studies have been conducted on eight sets of monozygous and nine sets of dizygous female Negro twins, both members of whom were heterozygous for G-6-PD deficiency. Twins were studied both by assay of erythrocytic G-6-PD activity and by the methemoglobin elution test (MET). The MET is a procedure which identifies histochemically cells with appreciable G-6-PD activity and permits accurate determination of the percentage of such cells in heterozygotes. Monozygous twins showed significantly less “within-pair” variation than dizygous twins with both the MET and G-6-PD assay.Concerning the significantly greater agreement in MET results in monozygous twins than dizygous twins, our present working hypothesis is that X-chromosomal inactivation in the Negro female is genetically controlled, rather than random. However, certain alternate hypotheses allowing for random X-inactivation have not been excluded; these include somatic cell selection after random X-inactivation, and cell exchange between identical twins in utero/it. Studies in nontwin related heterozygotes now underway should help differentiate among these various possibilities.In addition to the studies on 17 pairs of female twins heterozygous for G-6-PD deficiency, 26 pairs of nondeficient female Negro twins have been studied by G-6-PD assay. Within-pair variation in monozygous twins was significantly less than within-pair variation in dizygous twins in all cases. The genetic influences detected with the G-6-PD assay in the female twins could theoretically be due to nonrandom X-inactivation, to genetically determined quantitative differences in enzyme activity (e.g., isoalleles), or to both. By appropriate calculations, based on the MET results, we have factored out the effects of X-inactivation on overall enzyme activity in the heterozygous deficient twins. After removal of the effect of X-inactivation, monozygous twins heterozygous for enzyme deficiency continue to show significantly less within-pair variation than dizygous twins. This finding indicates significant genetic influences on quantitative G-6-PD activity other than X-inactivation and other than the deficiency allele. This conclusion has been strengthened by studies on male twins where X-inactivation is not present.

Relative Magnitudes of Crown Size Reduction and Body Size Reduction in 47-Trisomy G

Since crown size reduction has been observed in 47-trisomy G (M. M. COHEN and R. A. WINER, J Dent Res 44:197-208, 1965; M. M. COHEN, S. M. GARN, and M. A. GECIAUSKAS, J Dent Res 49:460, 1970) with delayed tooth formation timing (S. M. GARN, C. W. STIMSON, and A. B. LEWIS, J Dent Res 49:640, 1970), it is useful to compare the magnitude of crown size reduction with the magnitude of body size reduction characteristic of individuals with trisomy G (Downs syndrome) in general. Mesiodistal crown size data from 74 verified instances of 47-trisomy G (Walter E. Fernald State School, Waverley, Mass, USA) indicate