David Bixler

Familial branchio-oto-renal dysplasia: a new addition to the branchial arch syndromes.

The present report concerns a two‐generation family of nine individuals in which the father and three of the six living children all had: (1) a mixed hearing loss with a Mondini type cochlear malformation and stapes fixation; (2) cup‐shaped, anteverted pinnae with bilateral prehelical pits; (3) bilateral branchial cleft fistulas; and (4) bilateral renal dysplasia and anomalies of the collecting system. The father and one affected son also had aplasia of the lacrimal ducts. A fourth child who died at 5 months of age was reported to have branchial cleft fistulas and bilateral polycystic kidneys at autopsy. In addition, the concept of noso‐embryologic communities is presented. Such groups are composed of syndromes whose total phenotypic spectra not only overlap but also share common elements in embryogenesis. This concept is illustrated with a group of branchial arch syndromes that are related in this way.

Periodontosis: A phenotypic and genetic analysis☆

Two families who provide additional data concerning the metabolic, radiographic, and clinical parameters of periodontosis are presented. These findings include decreased serum alkaline phosphatase levels with absent liver isozyme fractions, decreased tubular bone over-all width and medullary space with relatively increased cortical area, and at least one case of primary dentition alveoloclasia with no permanent dentition alveoloclasia. In addition, a segregation analysis was performed on these two families and all completely reported families found in the literature. The results indicate that periodontosis is most probably inherited as an X-linked, dominant trait with decreased penetrance but relatively consistent gene expressivity. The female: male ratio of affected persons is approximately 2:1, and there is an over-all deficiency of males in these affected families.

The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome: Report of 2 cases and review of the literature

A search of the literature over the past 150 years reveals 19 proband cases of lobster claw deformity of the extremities and clefting of the primary and secondary palate. Some authors have reported that a few of these cases also have an atypical form of ectodermal dysplasia in which the skin is fair and the hair fine and light colored, and a tooth enamel dysplasia but normal salivary, sweat, and sebaceous gland function. Atresia of the lacrimal puncta may also be a part of this syndrome which has been designated the ectrodactyly‐ectodermal dysplasia‐clefting (EEC) syndrome. This report describes two unrelated females who appear to have the EEC syndrome, thereby bringing the total probable cases to five, two of which occurred in affected families (Walker & Clodius 1963, Cockayne 1936) and three of which were sporadic (Rudiger et al. 1970, this report). Dominant inheritance with incomplete penetrance is suggested.

Suggestion of linkage of a major locus for nonsyndromic orofacial cleft with F13A and tentative assignment to chromosome 6

A Danish material of 58 pedigrees with nonsyndromic orofacial cleft, selected out of a compre‐hensive Danish material for suggestiveness of autosomal dominant inheritance, was studied for linkage with 42 non‐DNA polymorphic marker Systems. Both cleft lip with or without cleft palate (CL(P)) and cleft lip alone (CP) were, for the purpose of linkage analysis, scored as if they were due to an autosomal dominant gène with complete penetrance. The highest lod score was with the blood clotting factor XIIIA (F 13A): for maies alone z=3.40 at theta = 0.00, for females alone z=0.30 at theta=0.21, and for these together z = 3.66 at theta=0.00 for males and 0.26 for females. Since F13A is known to be located distally on chromosome 6, we tentatively assign a major locus for orofacial cleft to this region. Since both CL(P) and CP pedigrees contribute to the positive score, the question arises whether this locus carries two cleft alleles.

Possible localization of a major gene for cleft lip and palate to 4q

Two of the 13 PCR markers were most informative in tentatively identifying a major gene for cleft lip on the q arm of chromosome #4 with a maximum LOD score of 2.27 (Ø= 0)

The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females

This report describes two families with the Nance‐Horan syndrome, an X‐linked trait featuring lenticular cataracts and anomalies of tooth shape and number. Previous reports have described blindness in affected males but posterior sutural cataracts with normal vision as the primary ocular expression in heterozygous females. In one of these two families, the affected female is not only blind in one eye but reportedly had supernumerary central incisors (mesiodens) removed. This constitutes the most severe ocular and dental expression of this gene in heterozygous females yet reported.

Phenotypic variation in the popliteal pterygium syndrome

At least 47 cases of the popliteal pterygium syndrome have been reported in the literature. Of these, 27 affected individuals were multiplex cases occurring in 10 families, while 20 were isolated cases: both dominant and recessive inheritance Of the trait have been proposed. This report documents the clinical variation in gene expression observed in a pair of affected monozygous twins, the first to be described with the syndrome. The marked phenotypic variation noted in the twins suggests that it will be difficult to distinguish genetic heterogeneity from variation in gene expression in this syndrome by clinical criteria alone. In the absence of knowledge of the primary gene defect, detailed examination of all first‐degree relatives of probands is essential for genetic counseling.

An incident of familial cancer, including 3 cases of osteogenic sarcoma.

Familial cancer is manifested by the early development of histologically different malignancies in multiple members of a family at different anatomical sites. Two or more generations must be involved. A family is presented in which 6 of 15 members, over 3 generations, developed 7 malignancies, of which 5 were distinctly different. Among these, osteogenic sarcomas appeared in successive generations. The explanation for this phenomenon may lie in hereditary susceptibility to living or nonliving carcinogens. An awareness of this entity will aid in early detection of malignancy in those affected and continued close observation of all members of a cancer family.

Cleft palate: A genetic and epidemiologic investigation

An examination of kindred histories of 561 Danish probands who have non‐syndromic CP has indicated that neither a multifactorial‐threshold model nor a single major locus model is completely compatible with the data. This suggests etiologic heterogeneity for CP, which was tested with kindred data.

Interradicular dentin dysplasia associated with amelogenesis imperfecta.

Very few reports are available on the occurrence of dysplasia of both enamel and dentin. This report concerns a rare association of amelogenesis imperfecta with a dysplasia of dentin in the interradicular area in sisters of Japanese descent who have no other morphologic anomalies. Retarded tooth eruption was also a clinical feature in both sisters. Histologic examination of several teeth revealed that the anomalous interradicular dentin consisted of a mass of small, onion-like calcified bodies. The absence of any dental abnormalities in both parents, who are related as first cousins, supports the concept of autosomal recessive inheritance for this trait.