ICNC Abstracts, ICNC 2018

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Whole Exome Sequencing (WES) identifies PGAP3 mutation in three patients from two Saudi families with hyperphosphatasia with mental retardation syndrome 4 (HPMRS4)

Last modified: 2018-09-09



Introduction: Hyperphosphatasia with mental retardation syndrome type 4 (HPMRS) is caused by recessive mutations in genes involved in the glycosylphosphatidylinsitol pathway, including PGAP3. It is a neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, hypotonia and dysmorphic features.

Methods: A description of the clinical presentation, neuroimaging findings of three patients from two families with mutation in PGAP3 gene

Results: Family 1: 3 years old boy is the first child to young consanguineous parents. Noticed from early infancy to have dysmorphic features in form of wide nasal bridge, cleft palate, microcephaly and nystagmus, together with central hypotonia, seizures and delayed speech.   Alkaline phosphatase level was always high (968 U/L). WES revealed PGAP3 mutation. MRI brain revealed retro-cerebellar cyst Family 2: Patient 1; 7 years old boy elder brother, from early infancy noticed to have global developmental delay, epilepsy, microcephaly, cleft palate and profound hypotonia.    Alkaline phosphatase level was high (933 U/L), and WES revealed PGAP3 mutation.    Patient 2: 12 months old boy, referred to the clinic with dysmorphic features   of low set ears, micrognathia, cleft palate, microcephaly, and hypotonia. His Alkaline phosphatase level was high (650 U/L), and WES revealed PGAP3 mutation. MRI brain revealed thin corpus callosum.

Conclusion: Hyperphosphatasia with mental retardation syndrome (HPMRS) should be considered in all cases of developmental delay, facial dysmorphism and elevated serum alkaline phosphatase. As an autosomal recessive disorder, families should be offered prompt genetic counseling.


Hyperphosphatasia; mental retardation; Alkaline phosphatase

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