Not all of the findings are present in any given patient. The first familial cases were reported in twins by Rosen and subsequently in 8 persons from a large three-generation pedigree by Pipkin. Moynahan first documented the association of the syndrome with cardiac abnormalities and short stature in 1962.
Hypotheses regarding the pathogenesis are speculative.
A mutation in the stem cell pool of the neural crest in embryonic life is regarded as a cause of cutaneous and neurologic defects. The cells derived from the neural crest form spinal and autonomic ganglion cells and the Schwann cells of peripheral nerves. They also take part in DOPA, epinephrine, and norepinephrine metabolism, which may result in abnormal skin pigmentation. As sympathetic terminations in cardiac ventricles are formed from neural crest derivatives, even the cardiac abnormalities of the syndrome are believed to be caused by the neural crest mutation. The syndrome seems to be rare both in the US and internationally.