**3. Results**

Considering the last 25 years of the Huntington Centre NRW, we identified 2593 individual patients suffering from HD and presenting in our outpatient and inpatient clinic for seeking medical advice or treatment.

Out of these 2593 patients, 32 individuals (Table 1) in total were identified with an early-onset of a manifest disease when younger than 21, which corresponds to a ratio of 1.23%. Children from all over Germany were admitted to the hospital. Dividing the 32 early-onset patients into pediatric and juvenile HD revealed 18 patients who were classified as pediatric (onset < 18 years of age) and 14 more being juvenile (18 < onset < 21 years of age). Therewith, the proportion of pediatric out of all HD patients presenting in our centre was identified as 0.69%.

**Table 1.** Clinical characteristics and relevant findings of juvenile and/ or pediatric Huntington's disease (HD) cases from the Huntington Centre, North













Patients are itemised to: individual patient number (numeric) and female (f) or male (m) sex, pediatric (P) or juvenile (J) onset, CAG repeat- expansion length, age of onset (years), age of diagnosis (years), paternal (P) or maternal (M) inheritance. Description of predominant challenging situation classified according to anamnesis (A), clinical examination (CE), further diagnostics (FD), socio-medical aspects (SM), treatment attempt (TA) and course of disease (CD). Abbreviation n.d. (no given data).

Considering the described cohort of early-onset patients, 59.4% appeared to be male patients. In the pediatric cohort, the rate of male patients (72.2%), corresponding to 13 out of 18 patients, was higher than in the juvenile cohort, where a lower rate of 42.9% (six out of 14 patients) appeared to be male.

Analyzing the early-onset cohort more closely revealed, 16 cases with a paternal inheritance model, seven cases with a maternal inheritance, two cases without any HD in the anamnesis of the accompanied parents or rest of the family anamnesis, and seven cases without given data from family anamnesis. As a reason for missing family history, detailed information from medical reports were not available any more in seven cases because reports were destroyed after the minimum of 10 years duty of archiving. The 23 cases with reported data from the family anamnesis therewith revealed a paternal inheritance of 69.6% in the monitored cohort.

The reported CAG repeat length of all early-onset patients (*n* = 25) revealed a median expanded allele length of 63. After diving into the different groups of pediatric (*n* = 14; M = 67.3; SD = 11.6) compared to juvenile HD patients (*n* = 11; M = 57.4; SD = 5.6), independent *t*-test (IBM® SPSS® Statistic V25, IBM Corp., Armonk, NY, USA) demonstrated significantly higher CAG repeats in the pediatric group (*t*(19.6) = −2,8, *p* = 0.011).

In the juvenile cohort, a mean age of onset (*n* = 14) was identified as 19.3 years (SD 0.9) and the age of diagnosis (*n* = 9) on average identified as 23.2 years (SD 1.2) (Table 2). The pediatric cohort revealed a mean age of onset (*n* = 16) of 10.3 years (SD 4.1) and an average age of diagnosis (*n* = 17) of 13.5 years (SD 3.8). Describing the cumulated percentages in the pediatric group revealed that 50% of the cohort had an onset ≤ 9 years of age and 75% of the cohort ≤ 13 years of age. Of the pediatric group, 52.9% was diagnosed with an age ≤ 13 years and 76.5% with an age ≤ 16 years.


**Table 2.** Demographics of the pediatric and juvenile HD cohort.

Comparing these median reported ages in juvenile and pediatric groups using independent t-tests demonstrated a significantly earlier onset (*t*(16.6) = 8.4, *p* ≤ 0.001) and diagnosis (*t*(21.4) = 9.1, *p* ≤ 0.001) in the pediatric group.

The mean times measured in years between age of onset and diagnosis revealed no significant difference between the pediatric (*n* = 15; M = 3.5; SD 1.9) and the juvenile group (*n* = 9; M = 3.0; SD 1.0) in the independent *t*-test (*t*(22) = −0.8, *p* = 0.411).

The motoric components of the disease manifestation revealed especially hypokinetic-bradykinetic compounds and rigidity being present in the majority of the pediatric cohort (reported in 11 out of 16 cases: 1, 2, 3, 5, 6, 7, 8, 9, 13, 14, 20) and also present in five out of nine cases with juvenile HD (cases 15, 18, 20, 23,24).

Six out of 16 pediatric cases (case 1, 2, 7, 8, 9, 20) revealed the presence of dystonia and therewith in 37.5% of the pediatric collective compared to 22.2% of juvenile cases (two of nine cases; cases 16, 24).

Hyperkinetic movement disorders in terms of chorea were present in cases 16, 18, 19, 21, 24 (all juvenile) and slightly in cases 22, 24 (both pediatric), which represents 55.6% of the juvenile and 12.5% of the described pediatric cohort. Another hyperkinetic movement disorder, myoclonus, was identified in two out of nine juvenile phenotypes (22.2% of the juvenile cohort).

Out of 16 pediatric patients, we identified six patients who were diagnosed with epilepsy, which corresponds to 37.5% of that pediatric cohort. In comparison, we identified two out of nine patients with epilepsy in the juvenile cohort (22.2% of the cohort).

Six out of 16 pediatric patients presented with tremor in their clinical assessments, which corresponds to 37.5% of the cohort. In the juvenile cohort one patient su ffered from tremor (11.1% of the cohort).

Changing and di fficulties of speech were present in cases 4, 6, 7, 13 (all pediatric) and case 17 (juvenile), and therewith relevant in 25% of the pediatric and 11.1% of the juvenile cohort.

Concerning the diversity of psychiatric problems, aggression and irritability was reported in 10 out of 16 pediatric cases (cases 2, 4, 5, 6, 11, 12, 13, 14, 22, 25), which corresponds to a ratio of 62.5%, and in three juvenile cases (cases 17, 18, 19), which is a ratio of 33.3% in the juvenile cohort. Suicidal ideations or attempts were described in eight cases in total, whereby five cases were pediatric (cases 2, 3, 5, 18, 22) and three cases were juvenile (cases 15, 17, 19), which reports a ratio of 31.2% in the pediatric and 33.3% in the juvenile group.

The presence of apathy in cases 2, 25 (both pediatric) as well as obsessive behavior in case 19 (juvenile) and 25 (pediatric) were described as other psychiatric symptoms.

The main aspects of social pediatric characteristics especially included problems in school, described in five pediatric cases (cases 2, 3, 4, 5, 6) and one juvenile case (case 7) as frequent initial symptoms, especially in the pediatric group and also accompanied with a cognitive decline (cases 1, 2, 9, 17).

Furthermore, other patients showed criminal behavior characteristics (case 6) as well as substantial problems with alcohol and drug abuse (cases 11, 13, 15) and serious problems concerning the social background and family, with violation and conflicts in the family (all pediatric cases 3, 11, 12, 14), which equates a ratio of 25% in the pediatric cohort.

Considering diagnostic interventions, five out of 16 pediatric patients (31.2%) and one juvenile case (21) had an MRI, whereby only in one case was an inconspicuous result reported.
