Lethal Pallister-Killian syndrome and Fryns syndrome: diagnostic considerations

Clinical similarities between Pallister-Killian and Fryns syndrome have been previously noted. A newborn with diaphragmatic hernia, diffuse corneal opacities, dysmorphic fades, and hypoplastic nails was believed to have Fryns syndrome. Chromosome analysis of peripheral lymphocytes showed 46, XY in 20 cells counted (525 band level). Despite maximal support, the baby remained unresponsive to therapy. Given the poor prognosis, it was agreed that respiratory support be discontinued. Autopsy confirmed a large left diaphragmatic defect/pulmonary hypoplasia, bilateral ureteral dilation, and intraventricular hemorrhage. Mild shortening of the upper limbs and cleft of the soft palate were also noted. Testicular tissue chromosome analysis showed isochromosome 12p in all 20 cells examined. There appears to be a subset of patients with Pallister-Killian who present in utero or neonatally with lethal manifestations. The most common cause of death in these individuals has been a large diaphragmatic hernia with resultant pulmonary hypoplasia. Although reports vary, the frequency of diaphragmatic hemia in lethal Pallister-Killian syndrome may be as high as 50%. We suspect that Pallister-Killian, lethal type, is underdiagnosed. Most routine cultured lymphocyte chromosome analyses will not demonstrate isochromosome 12p, leaving Fryns syndrome as the most likely diagnosis. Our case further substantiates the need for solid tissue chromosome examination in individuals with diaphragmatic hemia and other congenital anomalies.