(Kiosk 6) Rare PIGN Gene Mutation or Multiple Congenital Anomalies Hypotonia-seizures Syndrome 1 - A Case Report

Case Diagnosis: A 22-month-old boy with PIGN mutation (Multiple Congenital Anomalies Hypotonia-Seizures Syndrome 1).

Case Description or Program Description: The patient was born via C-section at 37 weeks to consanguineous parents. Birth was notable for low muscle tone, hypoglycemia and difficulty feeding necessitating NICU admission. Given his birth presentation, genetic testing was conducted which demonstrated multiple regions of homozygosity suggestive of uniparental disomy of Chromosome 7. Subsequent follow up evaluation showed persistent severe psychomotor delay, axial hypotonia, increased spasticity in UE and LE resulting in limb scissoring at rest. The patient underwent further genetic testing via whole exome sequencing which revealed homozygosity in the PIGN sequence.

Setting: Outpatient Developmental Pediatric Rehabilitation Clinic

Assessment/Results: Given the patient's deficits, the patient was started on early interventional therapies including physical, occupational, and speech & language therapy. Additionally, the patient was provided with custom bilateral AFO and a hip abduction brace with the goals of improving hip adduction, ankle range of motion, and improving truncal tone.

Discussion (relevance): There have been approximately seventy-six individuals with this mutation that have been described in the literature. Given the rarity of this disease there is limited information regarding PIGN mutations. The PIGN gene is involved in the biosynthesis of glycosylphosphatidylinositol (GPI) which plays an important role in anchoring various proteins to the cell membrane. Case reports have associated this condition with dysmorphic features, hypotonia, multiple congenital anomalies, cerebellar atrophy, severe developmental delay, encephalopathy, and premature seizures.

Conclusions: Mutations in the PIGN gene may represent an under-identified cause of developmental delay, early onset epilepsy, and hypotonia. Due to the small number of involved families worldwide, the prognosis is unknown and patients need close follow up. Physiatrists with awareness of this condition may play a significant role in early identification, and by providing essential interventions to improve developmental and functional outcomes, and ultimately improve quality of life.