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Rare Disease Diagnosis Resources

Resources and techniques for diagnosis of rare genetic disease.

Although no clinician can know 8000 rare diseases, they can recognise unusual patterns and explore when they see these.

Indeed, GPs are uniquely placed to help, offering whole patient care. As one of the few generalists working in the NHS and we are familiar with identifying the rare amongst the common, such as significant infections and cancers we may only see a handful of times in our career. We are exceptionally well placed to see the broader clinical picture and join the dots that may be missed by secondary care colleagues working in silos. The primary care electronic record (EHR) is a further valuable tool with continuity of clinical record over the life of the patients, the clues are frequently recorded and searchable and simply need to be joined together.

The Family-GENES Mnemonic for Scenarios to Suspect Rare or Genetic Disease

Family history: three generation family history. Multiple affected siblings or individuals in multiple generations. Absence of family history does NOT rule out genetic causes.
G: Group of congenital anomalies. Common anatomic variations are common; but two or more anomalies are much more likely to indicate the presence of a syndrome.
E: Extreme or Exceptional presentation. Early onset CV disease, cancer or renal failure. Unusually severe reaction to infectious or metabolic stress. Recurrent miscarriage.
N: Neurodevelopmental delay or degeneration. Developmental delay in the paediatric age group carries a very high risk for genetic disorders. Developmental regression in children or early onset dementia in adults should similarly raise suspicion for genetic aetiologies.
E: Extreme or Exceptional pathology.
S: Surprising laboratory values. Markedly abnormal pathology results.
Is there a more plausible explanation for my patient’s problems?

Taken from Whelan AJ, Ball S, Best L, Best RG, Echiverri SC, Ganschow P, Hopkin RJ, Mayefsky J, Stallworth J (2004) Genetic red flags: clues to thinking genetically in primary care practice. Prim Care 31:497-508, viii

Rare Disease Diagnostic Resources

These freely available online tools can be used to help refine a differential diagnosis when suspicions have been raised.

  • The Phenomizer. An online diagnostic engine where clinical terms using Human Phenotype Ontology (HPO) terms are combined to generate a differential diagnostic list.
  • Findzebra is a rare disease search engine that has been shown to outperform Google.
  • Orphanet, a European rare disease resource with information about diagnosis, diseases, genetics, and specialist centres.

What tools or resources do you find useful when you suspect a rare disease in a patient?

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Genomic Scenarios in Primary Care

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