The story of the Klein-Waardenburg syndrome begins with the presentation before the Swiss Society of Genetics in Geneva in August 1947 of a 10-year-old girl, who showed, in addition to deafmutism, partial albinism of the hair and over the whole body, dystopia canthorum, blue hypoplastic irides, broad and prominent nasal root, absence of the frontonasal angle, and blepharophimosis. Waardenburg, impressed by the complex clinical picture of our proposita whom he saw in Geneva in 1948, subsequently undertook a systematic investigation in several Dutch institutions for the deaf. He was able to confirm from his study that several manifestations of our patient, principally the palpebro-irido-auditory complex, represented a well-defined syndrome transmitted as a dominant trait with variable penetrance and expressivity. Since arthromyodysplasia did not figure among the clinical signs of his patients, Waardenburg suggested at first the possibility of either a homozygous state of the same mutation or the effect of a different allele as the cause of the accompanying gross skeletal and muscular defects. However, later on he completely questioned the nosologic placement of our case within the framework of his syndrome, having never encountered such extensive bone anomalies in more than one hundred observations.
Meanwhile four other cases with similar hypoplastic upper limb anomalies have been recorded and show an astonishing degree of resemblance to our original proposita with regard to specific bone alterations and their location. However, until recently there were still no observations concerning the inheritance of this complex syndrome.
The follow-up examination of a French family where the father manifested the complete Klein-Waardenburg syndrome including muscular and skeletal defects of the upper limbs, and his 12-year-old son who had apparently a typical Waardenburg syndrome (but with Sprengel deformity), enabled for the first time the postulation of a common genetic basis for both types with an autosomal-dominant inheritance of incomplete penetrance and variable expressivity. Further investigations are however needed before this type of inheritance can be considered as firmly established for the Klein-Waardenburg syndrome.