We report a 2-year-old boy with left congenital diaphragmatic defect (CDH), pulmonary hypoplasia, and polyhydramnios who harbors compound heterozygous mutations, c.1109A>G and c.2497_2498del, in the PIGO gene. The facial appearance was characterized by cloudy cornea, broad and flat nasal bridge, long philtrum, low-set ears, and micrognathia. Serum alkaline phosphatase level was consistently elevated, suggesting that he meets the criteria for Mabry syndrome. However, the observation of other anomalies including micropenis, cryptorchidism, and Hirschsprung disease suggests clinical features compatible with Fryns syndrome (FS). Left CDH and Hirschsprung disease were surgically repaired at 1 week and 3 months of age, respectively. He also exhibited multiple joint contractures and markedly decreased voluntary movement. Craw hands were seen but pes cavus was absent. Electrophysiology studies showed diffuse axonal demyelinating neuropathy. The cell surface expression of CD16, CD24, and CD59 on blood granulocytes was significantly reduced. The PIGO gene encodes ethanolamine phosphate transferase 3 in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. Mutations in the gene are known to cause Mabry syndrome, an inherited GPI deficiency (IGD) characterized by hyperphosphatasia. IGDs show clinical heterogeneity and overlap with other syndromes and diseases. A severe end of the phenotypic spectrum can be recognized as FS. This is the first report of PIGO gene mutations in a Mabry syndrome patient who also meets the criteria for FS.
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