Abstracts

Rationale: Temtamy syndrome is a genetic disorder caused by a mutation C1orf57 characterized by variable phenotypic expressivity with visual, cardio-vascular, brain malformations (Alrakaf et.al 2018). Phenotypic variations are seen at presentation to neurology services, as some patients have no seizures (sz) while others have intractable epilepsy with poor response to anti-seizure drugs (ASD), developmental delay, intellectual disability and speech delay.

We aim to study and understand the genotype and the variable phenotype of epilepsy in this syndrome, to identify any predictors of risk factors or contributors to the epilepsy, as there are no such studies reported previously looking at these variables.

Methods: This is an Institutional Review Board approved, multicenter, retrospective observational research study of 20 patients aged 0-14 yrs. All subjects were confirmed to have a genetic diagnosis of Temtamy Syndrome with + mutation C1orf57 gene on Epilepsy Genetic panel at King Faisal Specialist Hospital & Research Centre in Riyadh, in collaboration with other Tertiary Care centers, during 2008 to 2018.

Based on their + Genotype for C1orf57, they were further classified into three groups:
Group 1: C. 1A >G, P.Met1? Homozygous (Founder Mutation) (n= 15)
Group 2: C. 14-2A >G (Novel Mutation) (n=4)
Group 3: C. -3_2delins G (Novel Mutation) Frame Shift Mutation (n=1)

Results: Epilepsy & Genotypes: Our cohort showed 65% (n=13/20) had epilepsy, all had sz onset in infancy (Figure-1). 70% (9/13) had allele C. 1A >G, P.Met1 homozygous (Founder Mutation); 23 % (3/13) C. 53-2A >G (Novel Mutation); 7. 6 % (1/13) C.-3_2delins G (Novel Mutation) Frame Shift Mutation. Febrile sz (3/9, 33%) were seen exclusively in the Founder mutation group, with intractable Epilepsy + VNS installed in 1 patient (n=1).

Seizures Semiology: Most common Sz Semiology was Generalized Tonic clonic sz (100%), then Generalized Tonic sz (50%) Myoclonic 40% and least were Focal sz 10%.

Seizure Control: Well controlled sz were seen in (n=7) 53% managed on Monotherapy ASD (Figure -2).

Intractable Epilepsy: (n=6/13) 47% were on Polytherapy. 50% had the Founder mutation 3/6, (33%) had a Novel Mutation 2/6 and 1/6 (16%) Frame shift. 1 patient from the Founder mutation group had VNS installed.

EEG: Ten patient’s had Abnormal EEG (n=10/20) (50%), 1 patient had a normal EEG and 9 patient’s had no EEG. EEG did not record ictal activity. No Specific EEG pattern was seen in this syndrome, 50% of the studies (5/10 EEG’s) recorded: Generalized Spike and wave, slow Background & Multifocal spikes and polyspikes.

MRI abnormalities: N=9/13 (with sz) (69%) showed abnormal MRI findings with corpus callosum malformation. Additionally, 85% with MRI abnormality were in the Founder mutation group.

Conclusions: In patients with Temtamy syndrome, there is a spectrum seen in Epilepsy, with 65% having sz, with 47% having intractable Epilepsy (polytherapy, Abnormal EEG & VNS in 1). The Possible Risk factors and/or Predictors of Intractable Epilepsy in our cohort were found to be the presence of a C.1A >G, P. Met1 Homozygous (Founder mutation) with Febrile sz and/or Abnormal MRI brain.

Reference: AlRakaf et al: Am J Med Genet A. 2018 Mar; 176(3):715-721.

Funding: Please list any funding that was received in support of this abstract.: none.