Background and Aims:
The dystrophinopathy clinical labels ‘Duchenne’ and ‘Becker’ are often defined by the age of loss of ambulation (aLOA). However, many individuals receive these diagnoses based on other factors in advance of losing ambulation. Others may be given an “ambiguous” initial diagnosis. This study aims to explore the frequency of and contributing factors to receiving an ambiguous diagnosis or a diagnosis inconsistent with the person’s eventual phenotype.
Methods:
Data for 2128 male participants of The Duchenne Registry was reviewed. Participants self-reported their diagnosis as “Duchenne,” “Becker,” or “Duchenne or Becker, not yet certain” (ambiguous). Those with sufficient mobility data (N=819) were assigned a study diagnosis label of Duchenne, Presumably Duchenne, Becker, Presumably Becker, or Intermediate based on aLOA, assistive device use, and stair climbing ability. They were then categorized by whether there was a disparity between their self- and study-labeled diagnoses.
Results:
10.3% of participants self-reported an ambiguous diagnosis. The average age of diagnosis for those with an ambiguous diagnosis did not differ from those who self-reported a Duchenne diagnosis (p=0.25). Individuals with an ambiguous diagnosis had a higher proportion of non-truncating variants compared to those with self-reported Duchenne (p<0.001) and a lower rate of steroid receipt (p<0.001), even when both groups were limited to those with study label Duchenne (p=0.033).
9.52% of participants had a “diagnosis label conflict” between self- and study-labeled diagnoses. Those with self-reported Duchenne but study-label Becker were compared to those with a consistent label of Duchenne: these groups did not differ in average age of diagnosis (two-tail Welch’s t-test, p=0.21). Variants known to attenuate the Duchenne phenotype (del exon 45 and del exons 3-7) were found in higher proportion in the group with the diagnosis label conflict (p<0.001). Those with this label conflict also received steroids at a higher rate than those with a consistent Duchenne label (p=0.002).
Conclusions:
A relevant proportion of individuals report an ambiguous diagnosis or a diagnosis that does not reflect their eventual clinical course. Variant details may impact the rate of this experience. Ambiguous diagnosis may impact the treatment received. If clinical labels impact patient care, developing consistent practices for assigning diagnostic labels should be considered.