OpenLB
Open Library of Bioscience
Advanced Search
Movement disorders clinical practice
Dec 07, 2024;

No Evidence of Early Developmental Delay in Juvenile-Onset Huntington's Disease Patients.

Lucy Olson, Sarah Dickens, Jordan L Schultz, Mohit Neema, Peggy C Nopoulos
Author Information
  1. Lucy Olson: Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA.
  2. Sarah Dickens: Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA.
  3. Jordan L Schultz: Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA. ORCID
  4. Mohit Neema: Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA. ORCID
  5. Peggy C Nopoulos: Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City, Iowa, USA.
PMID: 39644245 DOI: 10.1002/mdc3.14287

Abstract

BACKGROUND: Previous studies suggest that early developmental delay is a common feature of Juvenile-Onset Huntington's disease (JOHD), with highest incidence in those with very high CAG repeats (> 80). However, all reports of developmental delay in JOHD are exclusively based on retrospective review of medical charts. Comprehensive assessment of birth history metrics may provide better insight into the question of early life development in JOHD.
OBJECTIVE: To explore the prevalence of prematurity, birth complications, low birth weight and developmental delay in patients with JOHD in comparison to control participants.
METHODS: Parents of patients with JOHD and gene-non-expanded (GNE) control participants from Kids-HD (n = 104) and Kids-JOHD (n = 34, 24% with CAG > 80) studies completed a comprehensive birth history questionnaire. Answers focused on prematurity, birth complications, and birth weight, and along with reports of early developmental milestones, were compared between groups.
RESULTS: There were no statistically significant differences in prematurity, birth weights, birth complications, or motor and verbal developmental milestones between JOHD patients and GNE controls (all P values > 0.1). Furthermore, stratifying JOHD patients by CAG expansion (low vs. high) also showed no significant differences (GNE vs. low or GNE vs. high).
CONCLUSIONS: These findings support the notion that JOHD does not manifest as developmental delay before motor symptom onset and highlight a new framework to understand the course and nature of the disease.

Keywords

Huntington's disease JOHD birth metrics developmental delay high CAG

References

  1. Nopoulos PC. Huntington disease: a single‐gene degenerative disorder of the striatum. Dialogues Clin Neurosci 2016;18(1):91–98.
  2. Schultz JL, Moser AD, Nopoulos PC. The association between CAG repeat length and age of onset of juvenile‐onset Huntington's disease. Brain Sci 2020;10(9):575.
  3. Bakels HS, Roos RAC, van Roon‐Mom WMC, de Bot ST. Juvenile‐onset Huntington disease pathophysiology and neurodevelopment: a review. Mov Disord 2022;37(1):16–24.
  4. Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington's disease. Nat Rev Neurosci 2005;6(12):919–930.
  5. Barnat M, Capizzi M, Aparicio E, et al. Huntington's disease alters human neurodevelopment. Science 2020;369(6505):787–793.
  6. Braz BY, Wennagel D, Ratié L, et al. Treating early postnatal circuit defect delays Huntington's disease onset and pathology in mice. Science 2022;377(6613):eabq5011.
  7. Hickman RA, Faust PL, Rosenblum MK, Marder K, Mehler MF, Vonsattel JP. Developmental malformations in Huntington disease: neuropathologic evidence of focal neuronal migration defects in a subset of adult brains. Acta Neuropathol 2021;141(3):399–413.
  8. van der Plas E, Schultz JL, Nopoulos PC. The neurodevelopmental hypothesis of Huntington's disease. J Huntingtons Dis 2020;9(3):217–229.
  9. Iennaco R, Formenti G, Trovesi C, et al. The evolutionary history of the polyQ tract in huntingtin sheds light on its functional pro‐neural activities. Cell Death Differ 2022;29(2):293–305.
  10. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntington's disease mutation: the sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994;330(20):1401–1406.
  11. Lee JK, Conrad A, Epping E, Mathews K, Magnotta V, Dawson JD, Nopoulos P. Effect of trinucleotide repeats in the Huntington's gene on intelligence. EBioMedicine 2018;31:47–53.
  12. Lee JK, Ding Y, Conrad AL, et al. Sex‐specific effects of the Huntington gene on normal neurodevelopment. J Neurosci Res 2017;95(1–2):398–408.
  13. Schultz JL, Neema M, Nopoulos PC. Unravelling the role of huntingtin: from neurodevelopment to neurodegeneration. Brain J Neurol 2023;146(11):4408–4410.
  14. Estevez‐Fraga C, Altmann A, Parker CS, et al. Genetic topography and cortical cell loss in Huntington's disease link development and neurodegeneration. Brain 2023;146(11):4532–4546.
  15. Schultz JL, van der Plas E, Langbehn DR, Conrad AL, Nopoulos PC. Age‐related cognitive changes as a function of CAG repeat in child and adolescent carriers of mutant huntingtin. Ann Neurol 2021;89(5):1036–1040.
  16. van der Plas E, Langbehn DR, Conrad AL, et al. Abnormal brain development in child and adolescent carriers of mutant huntingtin. Neurology 2019;93(10):e1021–e1030.
  17. Ungewitter E, Scrable H. Antagonistic pleiotropy and p53. Mech Ageing Dev 2009;130(1‐2):10–17.
  18. Osborne JP, Munson P, Burman D. Huntington's chorea. Report of 3 cases and review of the literature. Arch Dis Child 1982;57(2):99–103.
  19. Brooks DS, Murphy D, Janota I, Lishman WA. Early‐onset Huntington's chorea. Diagnostic clues. Br J Psychiatry 1987;151:850–852.
  20. Nahhas FA, Garbern J, Krajewski KM, Roa BB, Feldman GL. Juvenile onset Huntington disease resulting from a very large maternal expansion. Am J Med Genet A 2005;137A(3):328–331.
  21. Ruocco HH, Lopes‐Cendes I, Laurito TL, Li LM, Cendes F. Clinical presentation of juvenile Huntington disease. Arq Neuropsiquiatr 2006;64(1):5–9.
  22. Yoon G, Kramer J, Zanko A, Guzijan M, Lin S, Foster‐Barber A, Boxer AL. Speech and language delay are early manifestations of juvenile‐onset Huntington disease. Neurology 2006;67(7):1265–1267.
  23. Patra KC, Shirolkar MS. Childhood‐onset (Juvenile) Huntington's disease: a rare case report. J Pediatr Neurosci 2015;10(3):276–279.
  24. Latimer CS, Flanagan ME, Cimino PJ, et al. Neuropathological comparison of adult onset and juvenile Huntington's disease with cerebellar atrophy: a report of a father and son. J Huntingtons Dis 2017;6(4):337–348.
  25. Fusilli C, Migliore S, Mazza T, Consoli F, De Luca A, Barbagallo G, et al. Biological and clinical manifestations of juvenile Huntington's disease: a retrospective analysis. Lancet Neurol 2018;17(11):986–993.
  26. Schultz JL, Langbehn DR, Al‐Kaylani HM, van der Plas E, Koscik TR, Epping EA, et al. Longitudinal clinical and biological characteristics in juvenile‐onset Huntington's disease. Mov Disord 2023;38(1):113–122.
  27. DeLisi LE, Dauphinais ID, Gershon ES. Perinatal complications and reduced size of brain limbic structures in familial schizophrenia. Schizophr Bull 1988;14(2):185–191.
  28. Suman V, Luther EE, Preterm Labor NIH. [cited 2023]; Available from: 2022. https://pubmed.ncbi.nlm.nih.gov/30725624/.
  29. Osterman MJK, Hamilton BE, Martin JA, Driscoll AK, Valenzuela CP. Births: final data for 2021. Natl Vital Stat Rep 2023;72(1):1–53.
  30. Hollingshead A. Four Factor Index of Social Status. New Haven, CT: Yale University Department of Psychology; 1975.
  31. Martin JA, Hamilton BE, Osterman MJK. Births in the United States, 2022. NCHS Data Brief 2023;477:1–8.
  32. The Adolescent Brain Cognitive Development (ABCD) Study; [cited 2023]; Available from: https://abcdstudy.org/.
  33. Reasoner EE, van der Plas E, Al‐Kaylani HM, Langbehn DR, Conrad AL, Schultz JL, et al. Behavioral features in child and adolescent huntingtin gene‐mutation carriers. Brain Behav 2022;12(7):e2630.
  34. Golubev A, Hanson AD, Gladyshev VN. A tale of two concepts: harmonizing the free radical and antagonistic pleiotropy theories of aging. Antioxid Redox Signal 2018;29(10):1003–1017.
  35. Keenan K, Hipwell A, McAloon R, Hoffmann A, Mohanty A, Magee K. Concordance between maternal recall of birth complications and data from obstetrical records. Early Hum Dev 2017;105:11–15.
  36. Rice F, Lewis A, Harold G, et al. Agreement between maternal report and antenatal records for a range of pre and peri‐natal factors: the influence of maternal and child characteristics. Early Hum Dev 2007;83(8):497–504.

Grants

  1. 071108/CHDI Foundation
  2. R01 NS055903/NINDS NIH HHS
Journal Article

Word Cloud

Created with Highcharts 10.0.0JOHDbirthdevelopmentaldelayhighpatientsGNEearlyHuntington'sdiseaseCAGprematuritycomplicationslowvsstudiesJuvenile-OnsetreportshistorymetricsweightcontrolparticipantsmilestonessignificantdifferencesmotorBACKGROUND:Previoussuggestcommonfeaturehighestincidencerepeats>80HoweverexclusivelybasedretrospectivereviewmedicalchartsComprehensiveassessmentmayprovidebetterinsightquestionlifedevelopmentOBJECTIVE:exploreprevalencecomparisonMETHODS:Parentsgene-non-expandedKids-HDn = 104Kids-JOHDn = 3424%CAG > 80completedcomprehensivequestionnaireAnswersfocusedalongcomparedgroupsRESULTS:statisticallyweightsverbalcontrolsPvalues >01FurthermorestratifyingexpansionalsoshowedCONCLUSIONS:findingssupportnotionmanifestsymptomonsethighlightnewframeworkunderstandcoursenatureEvidenceEarlyDevelopmentalDelayDiseasePatients

Similar Articles

Cited By

No available data.