Hyperphosphatasia-mental retardation syndrome is a recently delineated disorder associated with a recognizable facial phenotype and brachytelephalangy. This autosomal recessive condition is caused by homozygous and compound heterozygous missense mutations of PIGV, encoding a member of the GPI-anchor biosynthesis pathway. Here, we report on two further, unrelated patients with developmental delay, elevated serum levels of AP, distinctive facial features, hypoplastic terminal phalanges, anal atresia in one and Hirschsprung disease in the other patient. By sequencing PIGV we detected compound heterozygous mutations c.467G>A and c.1022C>A in Patient 1 and a homozygous mutation c.1022C>A in Patient 2. We reviewed the eight reported cases with proven PIGV mutations and re-defined the phenotypic spectrum associated with PIGV mutations: intellectual disability, the distinct facial gestalt, brachytelephalangy, and hyperphosphatasia are constant features but also anorectal malformations and Hirschsprung disease as well as cleft lip/palate and hearing impairment should be considered as part of the clinical spectrum. Moreover, seizures and muscular hypotonia are frequently associated with PIGV mutations.
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