[MIM 239 300]

(Hyperphosphatasia with mental retardation type 1 syndrome, HPMRS 1)

Prevalence < 1/106. Autosomal recessive transmission of a mutation of the PIGV gene (1p36.11) (> 50 % of cases). Some cases are caused by a mutation of the PIGO or PGAP2 genes. This disease is also called HPMRS1  (acronym for HyperPhosphatasia with Mental Retardation Syndrome) and is part of the group of Hyperphosphatasias with mental retardation including:

• HPMRS1 [MIM 239 300], or Mabry syndrome: mutation of the PIGV gene (1p36.11)
• HPMRS2 [MIM 614 749], mutation of the PIGO gene (9p13);
• HPMRS3 [MIM 614 207], mutation of the PGAP2 gene (11p15);
• HPMRS4 [MIM 615 716], mutation of the PGAP3 gene (17q12);
• HPMRS5 [MIM 616 025], mutation of the PIGW gene (17q12);
• HPMRS6 [MIM 616 809], mutation of the PIGY gene (4q22).

Those mutations cause a disorder of the synthesis of glycosylphosphatidylinositol, a glycolipid anchoring more than 150 proteins to the cell surface.

Clinical synopsis:

-        severe mental retardation with absence of speech and motor retardation (sitting position, walking, ...)

-        hypotonia

-        epilepsy with tonicoclonic seizures

-        very significant elevation of the serum alkaline phosphatases level (2 to 20 times the normal level)

-        short terminal phalanges and hypoplastic nails

-        facial dysmorphism ; hypertelorism, broad base of the  nose with a rounded tip, rectangular facies, large palpebral fissures, thin "tent-shaped" upper lip  

Sometimes: cleft palate, congenital anorectal anomalies (anteriorly displaced anus), Hirschsprung disease, heart or urinary anomalies.

Anesthetic implications:

according to associated anomalies; mental retardation

References :

-        Abdel-Hamid MS, Issa MY, Otaify GA, Abdel-Ghafar SF, Elbendary HM, Zaki MS.
PGAP3-related hyperphosphatasia with mental retardation syndrome : report of 10 new patients and a homozygous founder mutation.
Clinical Genetics 2017 ; doi.org/10.1111/cge.13033

Update: November 2021