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Background: The appearance of the female breast viewed by mammography varies considerably from one individual to another because of underlying differences in the relative proportions of fat, connective tissue, and glandular epithelium that combine to create a characteristic pattern of breast density. An association between mammographic patterns and family history of breast cancer has previously been reported. However, this association has not been found in all studies, and few data are available on possible genetic components contributing to mammographic breast density. Purpose: Our purpose was to estimate familial correlations and perform complex genetic segregation analyses to test the hypothesis that the transmission of a major gene influences mammographic breast density. Methods: As part of a cohort study (initiated in 1944) of families with a history of breast cancer, the probands' female relatives who were older than 40 years were asked to obtain a routine mammogram. The mammograms of 1370 women from 258 independent families were analyzed. The fraction of the breast volume occupied by radiographically dense tissue was estimated visually from video displays of left or right mediolateral oblique views by one radiologist experienced in mammography who had no knowledge of individual relationships to the probands. Data on breast cancer risk factors were obtained through telephone interviews and mailed questionnaires. Unadjusted and adjusted familial correlations in breast density were calculated, and complex genetic segregation analyses were performed. Results: Sister-sister correlations in breast density (unadjusted and adjusted for age and either body mass index, menopausal status, hormone replacement therapy, waist-to-hip ratio, number of live births, alcohol consumption, or cigarette smoking status) were all statistically significant (r = .16-.27; all P [less than].05 [two-sided]). Estimated mother-daughter correlations were smaller in magnitude (r = .01-.17) and not statistically significant. Segregation analyses indicate that a major autosomal gene influences breast density. The mendelian transmission of a dominant gene provided the best fit to the data; however, hypotheses involving the inheritance of either a recessive gene or a codominant gene could not be ruled out. The mendelian dominant hypothesis, accounting for 29% of the variability in breast density, suggests that approximately 12% of the population would be expected to carry at least one variant allele of this putative gene. Women who inherit the variant allele would have a mean breast density about twice that of the rest of the population. Conclusions: Our preliminary findings suggest that, in this cohort of women at risk of breast cancer, mammographic breast density may be genetically influenced. [J Natl Cancer Inst 1997;89:549-556]

Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.

• Relatives of 125 probands, who had dementia of the Alzheimer type as proved by autopsy, were subjects of a genetic investigation. The relatives exhibited an excess of dementing illness consistent with genetic transmission. Risk to relatives decreased sharply as severity of the proband's illness decreased. Also, when compared with a control group and the general population, the relatives had excesses of Down's syndrome, lymphoma, and immune diatheses. These associated conditions also were more likely to be present when the proband had severe illness. Mortality at all ages was increased among the relatives.

The investigation was designed to explore the use of tests tapping reversible aspects of behavior and performance and to find out whether these data can be correlated with concurrent metabolic changes in different dietary phases. The four subjects had classic phenylketonuria, diagnosed on the basis of a high level of serum phenylalanine on a regular diet, and severe mental retardation. Three types of diet were used: the general institutional diet, a low phenylalanine diet, and a low phenylalanine diet with added L-phenylalanine. A position discrimination and reversal task was used. Blood samples were taken every week on the day before psychological testing, and one 24-hr urine sample was collected during each dietary phase.

MAROTEAUX and Lamy,1 in 1962, defined pycnodysostosis as a syndrome consisting of the following characteristics: (1) dwarfism; (2) osteopetrosis; (3) partial agenesis of the terminal digits of the hands and feet; (4) cranial anomalies, such as persistence of fontanelles and failure of closure of cranial sutures; (5) frontal and occipital bossing; and (6) hypoplasia of the angle of the mandible.The literature has revealed that several cases of this syndrome have been published as other disorders, chiefly Albers-Schönberg disease and cleidocranial dysostosis. Still others will be considered under differential diagnosis. The first reported case appears to be that of Montanari2 in 1923.Collado-Otero,3 in 1956, accurately described a case as "another form of osseous dystrophy," and credit should be given to this author as well as to Maroteaux and Lamy for their recognition of this disorder as a distinct entity. Our literature survey yielded a total of

THE holoprosencephalies form a spectrum of graded teratologic entities with cyclopia as the most extreme example. As a group, they exhibit anomalous development of the nose, mouth, eyes, ears, defective development of olfactory and optic structures, and impaired midline cleavage of the embryonic forebrain. In the extreme case, the cerebrum is a sphere with a single ventricle without corpus callosum or septum pellucidum. Most notable have been the studies of Goldstein,1 Yakovlev,2 and De Myer3,4 which have demonstrated that several median facial dysplasias exhibit the same brain alterations. Further interest was generated when it was shown that patients with trisomy D1 also exhibit many of these same changes. On the other hand, De Myer5 showed that infants having the same craniofacial stigmata but with few or trivial extracephalic malformations, had apparently normal karyotypes. Deletion of the short arm of chromosome 18 in cyclopia has been

A syndrome consisting of congenital absence of skin, affecting the lower extremities, blistering of skin and mucous membranes, and congenital absence and deformity of nails, is described in a kinship. The mode of inheritance is that of a fully penetrant, autosomal dominant gene. Expressivity of the syndrome is variable. Review of the congenital localized aplasias of skin and of the various forms of epidermolysis bullosa suggests that this may be a new syndrome.