Kym  Boyco(  PhD,  MD,  FRCPC,  FCCMG  Clinical  Gene*cist,  Children’s  Hospital  of  Eastern  Ontario  

Senior  Scien*st,  CHEO  Research  Ins*tute,  Professor  of  Pediatrics,  University  of  O@awa

Ontario’s  Rare  Disease  Strategy  

 Diagnosis  and  Preven.on  

Expert  Care  

Canadian  Access  to  Gene>c  Tes>ng  

CCMG  guidelines:      

Canadian  Posi>on  Statement  

J Med Genet 2015; 52: 431

CCMG  guidelines:    phenotype  or  family  history  suggests  singe-­‐gene  cause    muta*on  unknown  

Broad  Indica>ons  

Phenotype   High  degree  of  gene*c  heterogeneity      

Diagnos*c  odyssey    

Specific  gene*c  tests  have  failed  to  arrive  at  a  diagnosis    

 Cost  effec*veness   Genome-­‐wide   sequencing   is   a   more   cost-­‐effec*ve   approach   than   available   individual  or  gene  panel  tes*ng  

Ontario’s  Approach  

Direct  impact  on  clinical  decision-­‐making  and  care:    

•  Will  likely  preclude  further  invasive  diagnos*c  inves*ga*ons,  follow-­‐up,  or  screening  that  would  be  recommended  in  the  absence  of  tes*ng;  

•  Provides  specific  and  informed  reproduc*ve  decision  making  and  family  planning;  or,  

•  Will  enable  iden*fica*on  of  at  risk  family  members  to  iden*fy  if  they  carry  the  causa*ve  muta*on  and  facilitate  early  interven*on.  

   

   

Medically  Necessary:  

A  gene>c  e>ology  is  the  most  likely  explana>on:    

•  Moderate  to  severe  developmental  or  func*onal  impairment;  

•  Mul*system  involvement;  

•  Progressive  clinical  course  which  cannot  be  explained  by  another  cause;  or,  

•  Differen*al  diagnosis  includes  two  or  more  condi*ons.      

   

Indica>ons  for  Tes>ng  

Exclusion  Criteria:  1.  The  following  clinical  indica*ons  are  NOT  

an  indica*on  for  genome-­‐wide  sequencing:  •  Isolated  mild  intellectual  disability  or  

LD;  •  Nonsyndromic  au*sm;  or,  •  Isolated  neurobehavioural.  •  Isolated  neuropsychiatric  condi*ons  

2.  Pa*ent’s  phenotype  is  highly  specific  to  a  known  gene*c  condi*on  for  which  op*mized  gene*c  panel  tes*ng  exists.      

3.  Previous  comprehensive  panel  tes*ng  has  been  completed  in  the  last  3  years.  

   

WES  of  Family  Members  Sporadic  presenta*on  

•  Trio    

Consanguinity  •  Singleton    

Recessive  inheritance  suspected    •  One  affected  individual  and  an  unaffected  parent;  OR,    •  Two  affected  individuals  

X-­‐linked  inheritance    •  Singleton  with  filtering  for  X-­‐linked  variants    

Dominant  inheritance  •  2  most  distantly  related  family  members  

Next  Phase  of  Research  

Canada  is  the  best  place  on  earth  to  live  with  a  rare  disease.  

Every  child  and  family  in  Canada  with  RD  receives  a:  }  A  *mely  diagnosis  }  Op*mized  care  }  Pa*ent  and  family  empowerment  

Undiagnosed/Unrecognized Patient Pool

UDP Research

Rare    Flag  

Comm    Seq  

Clinical Genetics

Pa*ents  

Clinical Genetics

Therapies and Trials

CRISPR

Care Maps

Research

Research                

Diagnosed

Undiagnosed

Personalized Genomic Medicine

Patient Registries

Patients

Research

Rare Flag

Comm seq