Clinical Manifestation of Juvenile and Pediatric HD Patients: A Retrospective Case Series

Abstract

Background: Studies on the clinical manifestation and course of disease in children suffering from Huntington’s disease (HD) are rare. Case reports of juvenile HD (onset ≤ 20 years) describe heterogeneous motoric and non-motoric symptoms, often accompanied with a delay in diagnosis. We aimed to describe this rare group of patients, especially with regard to socio-medical aspects and individual or common treatment strategies. In addition, we differentiated between juvenile and the recently defined pediatric HD population (onset < 18 years). Methods: Out of 2593 individual HD patients treated within the last 25 years in the Huntington Centre, North Rhine-Westphalia (NRW), 32 subjects were analyzed with an early onset younger than 21 years (1.23%, juvenile) and 18 of them younger than 18 years of age (0.69%, pediatric). Results: Beside a high degree of school problems, irritability or aggressive behavior (62.5% of pediatric and 31.2% of juvenile cases), serious problems concerning the social and family background were reported in 25% of the pediatric cohort. This includes an attempted rape and robbery at the age of 12, as problems caused by the affected children, but also alcohol-dependency in a two-year-old induced by a non-HD affected stepfather. A high degree of suicidal attempts and ideations (31.2% in pediatric and 33.3% in juvenile group) was reported, including drinking of solvents, swallowing razor blades or jumping from the fifth floor with following incomplete paraparesis. Beside dopaminergic drugs for treatment of bradykinesia, benzodiazepines and tetrabenazine for treatment of dystonia, cannabinoids, botulinum toxin injection and deep brain stimulation were used for the improvement of movement disorders, clozapine for the treatment of tremor, and dopa-induced hallucinations and zuclopenthixole for the treatment of severe aggressive behavior. Conclusions: Beside abnormalities in behavior from an early age due to HD pathology, children seem to have higher socio-medical problems related to additional burden caused by early affected parents, instable family backgrounds including drug abuse of a parent or multiple changes of partners. Treatment required individualized strategies in many cases.

Juvenile‐Onset Huntington Disease Pathophysiology and Neurodevelopment: A Review

“…The most remarkable difference in clinical appearance between JHD and AHD is the higher prevalence of epileptic seizures in the JHD population, estimated to be 30% to 35%. Observational studies show it is far more common in childhood‐onset HD patients than in adolescent‐onset HD 8,13,30 . In AHD, the prevalence of epileptic seizures is comparable to population risk.…”

“…JHD patients are often difficult to diagnose 11,12 . This is mainly due to psychiatric and cognitive complaints that are easily misdiagnosed 9,11‐13 . Apart from the atypical clinical presentation, disease progression in childhood‐onset HD patients is faster and survival shorter compared to adult‐onset HD (AHD) 8 .…”

Differential Diagnosis of Chorea—HIV Infection Delays Diagnosis of Huntington’s Disease by Years

“…The treating physicians therefore suggested immediate genetic testing for HD mutation, which would have avoided misdiagnosis [49]. The early diagnosis of HD is not only academic, since this might result, apart from improved medical treatment, in amelioration of sociomedical care and financial support [50], as seen in our case following HD diagnosis.…”

Longitudinal Evaluation of the Effect of Tricyclic Antidepressants and Neuroleptics on the Course of Huntington’s Disease—Data from a Real World Cohort

“…However, the only US Food and Drug Administration-approved drug for treatment of chorea in HD is currently tetrabenazine and deutetrabenazine [ 9 ]. The situation is challenging for the treatment of other hyperkinetic movement-disorders such as dystonia or myoclonus with only case report series published for treatment recommendations [ 10 , 11 , 12 ] or predominant bradykinetic phenotypes especially in children [ 13 , 14 ]. Psychiatric symptoms such as depression and anxiety also lack standardized treatment strategies [ 15 ], often based on case reports or survey-based expert opinions with the aim to optimize individual therapeutic approaches [ 16 , 17 , 18 ].…”