Hyperphosphatasia with mental retardation syndrome 2 (HPMRS2)

(OMIM phenotype number #614749)

Hyperphosphatasia with mental retardation syndrome 2 (HPRMS2) is a rare autosomal recessive form of HPRMS  (see also HPMRS1) , and it is caused by compound heterozygous mutation in the PIGO gene. PIGO gene, such as PIGV gene,  is coinvolved in the glycosylphosphatidylinositol (GPI) anchor synthesis pathway, and PIGO mutations lead to a defect in GPI anchor synthesis with a consequent reduction in the level of GPI-anchored substrates such as serum alkaline phosphatase (ALP) localized at the cell surface. PIGO mutations have been identified in two families with HPMRS2 so far.

Gene

PIGO gene, 9p13.3 (OMIM gene/locus number #614730)

Phenotype

Moderately to severely delayed psychomotor development, mental retardation, various neurologic abnormalities such as seizures and hypotonia, hypoplastic or absent nails, long palpebral fissures, facial dysmorphism, and variable degrees of brachytelephalangy. Poor growth, microcephaly (1 patient), moderate to severe delayed speech and language development,  plagiocephaly (1 patient), coronal synostosis (1 patient), hypertelorism, short nose, broad nasal bridge and tip, tented mouth, atrial septal defect (1 patient), anal stenosis and atresia, vesicoureteral reflux (1 patient), broad halluces, and enlarged ventricles (1 patient).

Main biochemical alterations:

High ALP, high Pi, normal Ca, markedly high ALP, high acid phosphatase, high uric acid.

Image

Fig. (a) Facial appearance of a patient affected by HPRMS2 at the age of 15 years, and (b) an other patient (sister) at the age of 12 years. (c) Nail hypoplasia of the second and fourth digits and absent nail of the fifth digit. (d) Broad hallux, small nails of the second and third toes, and aplasia of the nails of the fourth and fifth digits.

Reproduced from Am J Hum Genet, Vol 91, Krawitz PM, Murakami Y, Hecht J, et al., Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation, Pages 146-51, Copyright 2012, with permission from Elsevier.

 

References

  1. Krawitz PM, Murakami Y, Hecht J, et al. Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation. Am J Hum Genet. 2012 Jul 13;91(1):146-51.
  2. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  3. http://www.omim.org