Understanding barriers to diagnosis in a rare, genetic disease: Delays and errors in diagnosing schwannomatosis

Abstract

Diagnosis of rare, genetic diseases is challenging, but conceptual frameworks of the diagnostic process can guide quality improvement initiatives. Using the National Academy of Medicine diagnostic framework, we assessed the extent of, and reasons for diagnostic delays and diagnostic errors in schwannomatosis, a neurogenetic syndrome characterized by nerve sheath tumors and chronic pain. We reviewed the medical records of 97 people with confirmed or probable schwannomatosis seen in two US tertiary care clinics. Time-to-event analysis revealed a median time from first symptom to diagnosis of 16.7 years (95% CI, 7.5-26.0 years) and median time from first medical consultation to diagnosis of 9.8 years (95% CI, 3.5-16.2 years). Factors associated with longer times to diagnosis included initial signs/symptoms that were intermittent, non-specific, or occurred at younger ages (p < 0.05). Thirty-six percent of patients were misdiagnosed; misdiagnoses were of underlying genetic condition (18.6%), pain etiology (16.5%), and nerve sheath tumor presence/pathology (11.3%) (non-mutually exclusive categories). One-fifth (19.6%) of patients had a clear missed opportunity for genetics workup that could have led to an earlier schwannomatosis diagnosis. These results suggest that interventions in clinician education, genetic testing availability, expert review of pathology findings, and automatic triggers for genetics referrals may improve diagnosis of schwannomatosis.

Keywords: delayed diagnosis; diagnostic errors; missed diagnosis; rare disease; schwannomatosis.

Figure 1

Conceptual Model of the Diagnostic Process (Reprinted with Permission from the National Academy of Medicine)

Figure 2.

Key Diagnostic Timepoints and Diagnostic Intervals

Figure 3.

Timeliness of Schwannomatosis Diagnosis Probability of receiving a schwannomatosis diagnosis based on time to diagnosis of confirmed schwannomatosis patients (n=64, red); time to diagnosis communication in confirmed patients with documented communication (n=54, blue); and total time spent in the diagnostic process for all the entire cohort (n=97, green).