OMIM ID:
Hyperphosphatasia with Mental Retardation Syndrome 6
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Congenital cataracts may be present. The eyes appear deeply-set and strabismus has been seen in severely affected cases.
Systemic Features
Two families have been reported. The range of severity in symptoms is wide. Birth may occur prematurely especially in the presence of polyhydramnios. Postnatal development can be complicated by seizures, chronic lung disease, developmental regression, and renal disease. Poor growth secondary to feeding difficulties have been reported. Death can occur in early childhood.
Dysmorphic features include a short neck, bitemporal narrowing, depressed nasal bridge, and proximal limb shortening. Osteopenia, flexion contractures, and hip dysplasia may be present. Dilatation of the renal collecting system with increased echogenicity have been reported. Creatine kinase and serum alkaline phosphatase may be increased and muscle histology shows small, atrophic fibers with increased fibrosis and considerable variations in fiber size.
Genetics
Inheritance
Homozygous mutations in the PIGY gene (4q22.1) resulting in deficiencies of glycosylphosphatidylinositol synthesis have been associated with this condition.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.