Among the multiple congenital anomalies (MCA) syndromes, the Noonan syndrome (NS) is a cardiofacial syndrome in which affected individuals may be short and mildly mentally retarded. Autosomal dominant inheritance of Noonan syndrome with variable expressivity has been documented in many families. Genetic heterogeneity has been postulated in Noonan syndrome because of the wide phenotypic variability, the relatively high incidence, and the occasional recurrence in sibs with apparently normal parents. Clinical variability is usual in autosomal dominant disorders, and mildly affected individuals may be difficult to recognize as gene carriers. Thus, a family with two or more affected children may simulate autosomal recessive inheritance. We have studied serial and family photographs of NS individuals in order to assess the likelihood of gene carriers' being missed in genetic studies. We have confirmed wide clinical variability within families, and more importantly, we have documented marked change of phenotype with age from the newborn period, infancy, childhood, and adolescence to adulthood. Manifestations in adults may be subtle and some without a known heart defect or other medically significant problems may have been considered normal in the past. Our study, while not ruling out causal heterogeneity, suggests that the change of phenotype with age may have been falsely perceived as clinical heterogeneity. A particular and subtle phenotype must be searched for in parents of affected children.

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Fifty‐two patients referred for suspicion of the Williams syndrome have been evaluated and divided into those with and without the syndrome by numerical analysis. A diagnostic index using 50 characters separates patients into two groups with an expected accuracy of 99%. An index using 40 of the characteristics is expected to be applicable to young infants without a substantial decrease in accuracy.

Short trunk dwarfism involving skeletal anomalies of vertebrae and ribs have been reported under various names. Both dominant and recessive and severe and mild conditions are found. We report on a patient without a severe handicap by age 3 years despite severe involvement of the thorax at birth, suggesting that a more complete classification of such anomalies is needed for counseling. We have used an objective method to classify 39 informative patients from the literature, 35 said to have a recessive disease and four a dominant one. Two patients with the costovertebral segmentation defect with mesomelia (COVESDEM) syndrome were added for comparison with our patient. The results of cluster analysis show that there are three phenotypic groups of patients. Cluster 1 contains 19 patients with a severe form of spondylothoracic dysplasia; cluster 2 includes patients with a mild autosomal recessive and a dominant type; cluster 3 groups the two sibs with the COVESDEM syndrome and our patient. One must be cautious in advising families of the prognosis for a child with severe structural chest deformity since it may not be severe from a functional point of view. More data are needed for complete discrimination between the mild autosomal recessive and dominant forms.

We have classified patients referred for suspicion of the Brachmann-De Lange syndrome (BDLS) into two groups using techniques of numerical taxonomy. Patients with the syndrome share an array of abnormal characteristics, and those without it have different abnormal characteristics. A group of 30 characters that best distinguish the two groups of patients was used to construct a diagnostic index. The index score is expected to divide 99% of patients into those with and without the syndrome, leaving 1% in a "zone of doubt." All 46 patients used to construct the index and 16 new patients had scores in either the BDLS or non-BDLS range and none were in the zone of doubt. A previously published index using metacarpal-phalangeal measurements, although less discriminatory, confirmed our findings in 84% of 25 patients tested, the remainder having scores in the zone of doubt for that index.