IllnessMentale Retardierung mit Hyperphosphatasie, Differentialdiagnose

NGS +

Hyperphosphatasia with mental retardation (e.g. Mabry and Chime syndrome) is characterized by moderate to severe intellectual disability, prominent facial features, hyperphosphatasia and possibly other symptoms. These patients typically have little or no language development and are delayed in the development of motor skills. Some affected individuals are hypotonic and develop epilepsy in early childhood, usually of the generalized tonic-clonic type. Hyperphosphatasia begins within the first year of life. Affected individuals usually have elevated levels of alkaline phosphatase in the blood. The elevated enzyme levels remain relatively stable throughout life. Isolated hyperphosphatasia does not appear to have any other adverse health effects. The least severely affected individuals have only mental retardation and hyperphosphatasia. Other common features include brachytelephalangia, nail hypoplasia and anal stenosis/atresia or Hirschsprung disease and rarely hearing loss. Symptoms vary among affected individuals. Mutations in the PIGV, PIGO, PGAP2, and 4 related genes cause hyperphosphatasia with mental retardation. These genes are all involved in the synthesis of glycosylphosphatidylinositol (GPI) anchors. Mutations in the PIGV gene are the most common cause and account for about half of cases. Mutations in the PIGO, PGAP2 and the few other genes involved each account for only a small proportion of cases. Hyperphosphatasia with mental retardation is inherited in an autosomal recessive manner. The DNA diagnostic yield is not known. Therefore, negative molecular genetic results do not exclude clinical diagnosis.

Reference: https://medlineplus.gov/genetics/condition/mabry-syndrome/

• CHIME [Coloboma, cong. Heart defects, migratory Ichthyosiform dermatosis, MR, Ear anom.] s. (PIGL)
• Glycosylphosphatidylinositol biosynthesis defect 11 (PIGW)
• Hyperphosphatasia with mental retardation syndrome 1 (PIGV)
• Hyperphosphatasia with mental retardation syndrome 2 (PIGO)
• Hyperphosphatasia with mental retardation syndrome 3 (PGAP2)
• Hyperphosphatasia with mental retardation syndrome 4 (PGAP3)
• Hyperphosphatasia with mental retardation syndrome 5 (PIGW)
• Hyperphosphatasia with mental retardation syndrome 6 (PIGY)
• Zunich neuroectodermal syndrome (PIGL)