Abstract
Two adolescent female patients, who were referred independently of each other, presented
with progressive gait disturbances that worsened over the course of the day. Symptoms
began in early childhood with foot instability and progressed to clubfoot, pain, and
limping. MRI of the neuroaxis did not reveal any central nervous system abnormalities.
Genetic testing identified the same intronic variant of uncertain significance in
GCH1 in both individuals. Subsequent investigations uncovered a previously unrecognized
familial relationship between the two patients, belonging to an extended family in
which six women were affected by a gait disorder. Previous diagnoses within the family
included childhood-onset spasticity and psoriatic arthritis. The familial GCH1 variant
was confirmed in all symptomatic individuals, as well as in two asymptomatic female
carriers. RNA sequencing revealed a splicing defect caused by the GCH1 near splice-site
variant. A robust clinical response to L-DOPA therapy confirmed the diagnosis of DOPA-responsive
dystonia (DRD) in this family. This case highlights the phenotypic variability of
DRD, which frequently leads to misdiagnosis and delays in appropriate treatment. Careful
assessment of family history and recognition of diurnal symptom fluctuations are key
to identifying this highly treatable condition.
Keywords
DRD - GCH1 - Segawa syndrome
