NOONAN SYNDROME - THE CHANGING PHENOTYPE

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 2 or more affected children may simulate autosomal ecessive inheritance. Serial and family photographs of NS individuals were studied in order to assess the likelihood of gene carriers'' being missed in genetic studies. Wide clinical variability within families was confirmed and more importantly, marked change of phenotype with age from the newborn period, infancy, childhood, and adolescence to adulthood was documented. Manifestations in adults may be subtle and some without a known heart defect or other medically signficant problems may have been considered normal in the past. The study, while not ruling out causal heterogeneity, suggests that the change of phenotype must be searched for in parents of affected children.