Both Paget disease and the group of rare Paget-like skeletal disorders including expansile skeletal hyperphosphatasia
, familial expansile osteolysis, juvenile Paget disease, and fibrous dysplasia are characterized by a substantial increase in nearly every BTM measured (92).
To date, mutations in six genes (PIGV, PIGY, PIGO, PGAP2, PIGW, and PGAP3) have been shown to cause hyperphosphatasia with mental retardation syndrome (HPMRS) in an autosomal recessive mode of inheritance (no autosomal dominant mutations have been reported thus far).
Of the six genes previously shown to cause hyperphosphatasia with mental retardation syndrome (HPMRS), only one lies within any of these homozygous loci: PGAP2, located at position chr11:3,819,0493,847,601, residing within the chromosome 11 locus (Table 2).
Here we describe an autosomal recessive form of hyperphosphatasia with mental retardation syndrome (HPMRS).
Mutations in six different genes (PIGV, PIGY, PIGO, PGAP2, PIGW, and PGAP3) involved in GPI-anchor biosynthesis have been shown to cause hyperphosphatasia with mental retardation syndrome (HPMRS).
Krawitz and colleagues identified mutations in PIGV by exome sequencing of DNA samples from three individuals with hyperphosphatasia with mental retardation syndrome (HPMRS, also termed Mabry syndrome).
Murakami proposed a mechanism for the hyperphosphatasia based on an in vitro study with PIGV-defective CHO cells.
Therefore, the mechanisms of secretion or hyperphosphatasia in PIGV/PIGO-defective cells and PGAP2-defective cells are different, comprising secretion before and after attachment of GPI, respectively.
Increased bone density with diaphyseal involvement Diaphyseal Craniotubular AD dysplasia, sclerosis, Camurati-Engelmann symmetrical Craniodiaphyseal Craniotubular AR, AD dysplasia Lenz Majewski Craniotubular SP dysplasia Endosteal Craniotubular hyperostosis sclerosis, symmetrical van Buchem type AR Worth type AD sclerosteosis AR with cerebellar AR hypoplasia Kenny Cafey Diaphyseal AD, AR dysplasia cortex Osteoectasia with Craniotubular AR hyperphosphatasia
sclerosis, (juvenile Pagets) bowing Diaphyseal dysplasia Diaphyseal AR with anaemia cortex Diaphyseal medullary Diaphyseal AD stenosis with bone cortex malignancy (Hardcastle) 3.
Similar conditions include rare bone dysplasias like hyperphosphatasia, Engelmann disease, osteopetrosis and fibrogenesis imperfecta.
* Hyperphosphatasia (juvenile Paget disease) in young patients.
Juvenile Paget disease, also called hereditary hyperphosphatasia or hyperostosis corticalis deformans juvenilis, has some similarities to adult Paget disease, but it has different morphological characteristics.