Action Myoclonus-Renal Failure (AMRF) syndrome is a rare subtype of progressive myoclonic epilepsy. It is an autosomal recessive disease caused by biallelic, loss-of-function pathogenic variants in the gene SCARB2. Neurological symptoms include action myoclonus, ataxia, and tremor, but notably with preservation of cognition as compared to other myoclonic syndromes. 

23 year old woman with uncomplicated birth and developmental history first developed tremors in left hand with fine movements at age 17. Symptoms rapidly progressed to myoclonic jerks in all extremities and trunk, leaving her wheelchair dependent after 1.5 years since symptom onset. Five years after her symptom onset, she was incidentally found to have renal failure requiring hemodialysis, but this did not improve her symptoms. 

MRI of the brain and spine, electrodiagnostic studies were normal. Renal biopsy showed advanced focal-segmental glomerulosclerosis with collapsing variant. First EEG performed after 2 years of symptom onset was normal. Repeat EEG obtained 4 years after symptom onset showed intermittent sharp waves in bi-temporal, centroparietal areas. Seven years after symptom onset, EEG showed near continuous trains of irregular bilaterally-synchronous 2-3 Hz polyspike-wave complexes. 

Patient was diagnosed with AMRF syndrome after gene sequence analysis identified two heterozygous mutations in the SCARB2 gene: c.434_435dup (p.Trp146Serfs*16) ----- c.435_436insAG (W146SfsX161) and c.1187+2dup(intronic) ----- c.1187+3insT.

We report a case of AMRF syndrome caused by a novel combination of heterozygous gene mutation in SCARB2 gene. Reason for variable phenotypic presentation in patients with AMRF syndrome is unclear. But efforts to recognize and elucidate SCARB2 genotype-phenotype correlation may be important. There was tremendous delay in diagnosis and a functional disorder was once contemplated which delayed the symptomatic treatment in this progressive syndrome.