Objective:

To study the natural history of motor, cognitive development and mood in early onset hereditary spastic paraplegias herein called e-HSP.

Background:

e-HSP is a heterogeneous group of ultra-rare genetic diseases with the uniting clinical feature of lower limb spasticity and weakness presenting in childhood. However, little is known of the early development and psychological manifestations of e-HSP. Here we outline 87 patients with e-HSP and their early childhood development, cognitive function and mood.

Design/Methods:

Retrospective analysis of 87 genetically confirmed e-HSP patients, the majority with SPG4 and SPG3A mutations.  Patients were consented and clinical information was collected at each clinic visit including developmental history, school performance and mood.  Patients and families were contacted or met with in person to validate missing data points.  

Results:

Two thirds of patients with e-HSP were found to have average to high cognitive function and perform well academically. Even 50% of patients who also had a confounding diagnosis of a neurodevelopmental or learning disorder were able to enroll in regular and advanced placement courses in school.  25% of patients had attention deficit disorder.  Many of the patients had reported experiencing sadness around their diagnosis and 25% of patients reported being diagnosed with an emotional disorder such as anxiety or depression. Within SPG3A, 8/18 required assistance with long distances including a walker or wheelchair. Within SPG4, patients with de novo mutations showed a severe early developmental disorder.  However, no genetic differences could be discerned in patients who had motor progression to walker or wheelchair use. Other mutations of SPG were included in this cohort but limited n-values confounded analysis on specific mutations. 

Conclusions:

For the majority of e-HSP patients, motor disorder is the predominant disease feature, but patients should be screened for attention deficit, anxiety, and depression.