(HPMRS)

HPMRS acronym for :HyperPhosphatasia with Mental Retardation Syndrome

Subclass of the congenital disorders of glycosylation of proteins. Autosomal recessive transmission. Diseases where mental retardation is associated with elevated alkaline phosphatases levels. Those diseases are due to a disorder of the synthesis, transfer or transformation of glycosylphosphatidylinositol (PIG or PGAP genes), a glycolipid anchoring more than 150 proteins on the cell surface. Due to the absence of specific biological marker, the diagnosis is difficult and often late.

The lack of anchoring of liver alkaline phosphatases leads to elevated  alkaline phosphatases levels in the blood.

Different types of HPMRS are known:

-        HPMRS1 [MIM 239 300] due to a mutation of the PIGV gene (1p36.11): see Mabry Syndrome

-        HPMRS2 [MIM 614 749] due to a mutation of the PIGQ gene (9p13): mental retardation, hypotonia, seizures, hypoplastic  nails, heart defect, facial dysmorphism

-        HPMRS3 [MIM 614 207] due to a mutation of the PGAP2 gene (11p15.4): mental retardation, seizures, facial dysmorphism

-        HPMRS4 [MIM 615 716] due to a mutation of the PGAP3  gene(17q12): severe mental retardation, epilepsy, postnatal microcephaly, facial dysmorphism (hypertelorism, broad nose, big ears, arched eyebrows, large palpebral fissures), cleft palate, sometimes double row of teeth or congenital heart disease

-        HPMRS5 [MIM 616 025] due to a mutation of the PIGW gene (17q12): developmental retardation, West syndrome, facial dysmorphism

-        HPMRS6 [MIM 616 809] due to a mutation of the PIGY gene (4q22) variable phenotypes

Other mutations lead to various pathologies where there is no elevated alkaline phosphatases level:

-        CHIME syndrome (acronym of Colobomas -Heart disease -Ichtyosiform dermatosis -Mental retardation and Ear anomalies) or Zunich neuroectodermic syndrome (PIGL gene): coloboma, ichtyosiform dermatosis, mental retardation, congenital heart disease

-        MCAHS syndrome (acronym for Multiple Congenital Anomlies -Hypotonia -Seizures) (PIGN gene): hypotonia, seizures, progressive cerebellar atrophy, multiple congenital anomalies

-         X-linked MCAHS2 syndrome (IAMP gene): convulsions, cerebral malformations, cleft palate, hypotonia and contractures

-        MCAHS3 syndrome (PIGT gene): hypotonia, seizures, facial dysmorphism, ophthalmic, endocrine and skeletal abnormalities, hypophosphatasia

-        PIGM-CDG syndrome (PIGM gene): portal vein thrombosis

Anesthetic implications:

management of an hypotonic child with epilepsy and more or less severe mental retardation

References :

-        Jezela-Stanek A, Ciara E, Piekutowska-Abramczuk D et al. Congenital disorders of glycosylphosphatidylinositol (GPI-anchor biosynthesis - The phenotype of two patients with novel mutations in the PIGN and PAGP2 genes. Eur J Paediatr Neurol 2016; 20: 462-73.

-        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 2017