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Neurodevelopmental disorder with hyperkinetic movements and dyskinesia(NEDHYD)

MedGen UID:
1794248
Concept ID:
C5562038
Disease or Syndrome
Synonyms: NEDHYD; NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA
 
Gene (location): ADCY5 (3q21.1)
 
Monarch Initiative: MONDO:0859211
OMIM®: 619651

Definition

Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) is an autosomal recessive complex neurologic disorder characterized by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders (summary by Okamoto et al., 2021 and Kaiyrzhanov et al., 2021). [from OMIM]

Clinical features

From HPO
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Compulsive behaviors
MedGen UID:
109373
Concept ID:
C0600104
Mental or Behavioral Dysfunction
Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Delayed ability to roll over
MedGen UID:
1718874
Concept ID:
C5397980
Finding
Delayed achievement of the ability to roll front to back and back to front.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

Professional guidelines

PubMed

Drug Ther Bull 1995 Aug;33(8):57-60. doi: 10.1136/dtb.1995.33857. PMID: 8529539
Ware JC
J Clin Psychiatry 1983 Sep;44(9 Pt 2):25-8. PMID: 6355074
Lambert NM, Windmiller M, Sandoval J, Moore B
Am J Orthopsychiatry 1976 Apr;46(2):335-52. doi: 10.1111/j.1939-0025.1976.tb00933.x. PMID: 4973

Recent clinical studies

Etiology

Robison LM, Sclar DA, Skaer TL, Galin RS
Clin Pediatr (Phila) 1999 Apr;38(4):209-17. doi: 10.1177/000992289903800402. PMID: 10326176
Taylor EA
Br J Psychiatry 1986 Nov;149:562-73. doi: 10.1192/bjp.149.5.562. PMID: 3545357
Rie HE
Am J Dis Child 1975 Jul;129(7):783-9. doi: 10.1001/archpedi.1975.02120440009003. PMID: 1146773
Stores G
Dev Med Child Neurol 1975 Oct;17(5):647-58. doi: 10.1111/j.1469-8749.1975.tb03536.x. PMID: 241674
Sroufe LA, Stewart MA
N Engl J Med 1973 Aug 23;289(8):407-13. doi: 10.1056/NEJM197308232890806. PMID: 4146358

Diagnosis

Lenka A, Jankovic J
Tremor Other Hyperkinet Mov (N Y) 2023;13:8. Epub 2023 Mar 28 doi: 10.5334/tohm.758. PMID: 37008994Free PMC Article
Taylor EA
Br J Psychiatry 1986 Nov;149:562-73. doi: 10.1192/bjp.149.5.562. PMID: 3545357
Merifield DO, Hall CM, Merrell HB
Ann Otol Rhinol Laryngol 1976 Mar-Apr;85(2 pt.1):255-9. doi: 10.1177/000348947608500210. PMID: 1267329
Rie HE
Am J Dis Child 1975 Jul;129(7):783-9. doi: 10.1001/archpedi.1975.02120440009003. PMID: 1146773
Schain RJ
Curr Probl Pediatr 1975 Aug;5(10):3-30. doi: 10.1016/s0045-9380(75)80007-7. PMID: 1101714

Therapy

Baldessarini RJ
Dis Mon 1977 Nov;24(2):1-65. doi: 10.1016/s0011-5029(77)80016-3. PMID: 21061
Rie HE
Am J Dis Child 1975 Jul;129(7):783-9. doi: 10.1001/archpedi.1975.02120440009003. PMID: 1146773
Schain RJ
Curr Probl Pediatr 1975 Aug;5(10):3-30. doi: 10.1016/s0045-9380(75)80007-7. PMID: 1101714
Barker P
J Child Psychol Psychiatry 1975 Apr;16(2):169-72. doi: 10.1111/j.1469-7610.1975.tb01266.x. PMID: 1055116
Stores G
Dev Med Child Neurol 1975 Oct;17(5):647-58. doi: 10.1111/j.1469-8749.1975.tb03536.x. PMID: 241674

Prognosis

Lenka A, Jankovic J
Tremor Other Hyperkinet Mov (N Y) 2023;13:8. Epub 2023 Mar 28 doi: 10.5334/tohm.758. PMID: 37008994Free PMC Article
Matson JL, Gorman-Smith D
Appl Res Ment Retard 1986;7(1):95-103. doi: 10.1016/0270-3092(86)90021-4. PMID: 3516069
Merifield DO, Hall CM, Merrell HB
Ann Otol Rhinol Laryngol 1976 Mar-Apr;85(2 pt.1):255-9. doi: 10.1177/000348947608500210. PMID: 1267329
Sroufe LA, Stewart MA
N Engl J Med 1973 Aug 23;289(8):407-13. doi: 10.1056/NEJM197308232890806. PMID: 4146358
Freeman RD
Prog Neurol Psychiatry 1968;23:454-68. PMID: 4237913

Clinical prediction guides

Levy JD, Kronenberger WG, Dunn DW
J Atten Disord 2017 May;21(7):575-586. Epub 2013 Aug 30 doi: 10.1177/1087054713497792. PMID: 23995051
Imeraj L, Antrop I, Roeyers H, Deboutte D, Deschepper E, Bal S, Sonuga-Barke E
J Atten Disord 2016 Jan;20(1):71-81. Epub 2013 Apr 2 doi: 10.1177/1087054713478464. PMID: 23548869
D'Urso G, Bruzzese D, Ferrucci R, Priori A, Pascotto A, Galderisi S, Altamura AC, Bravaccio C
World J Biol Psychiatry 2015;16(5):361-6. Epub 2015 Mar 24 doi: 10.3109/15622975.2015.1014411. PMID: 25800799
Matson JL, Gorman-Smith D
Appl Res Ment Retard 1986;7(1):95-103. doi: 10.1016/0270-3092(86)90021-4. PMID: 3516069
Stores G
Dev Med Child Neurol 1975 Oct;17(5):647-58. doi: 10.1111/j.1469-8749.1975.tb03536.x. PMID: 241674

Recent systematic reviews

Rizzo G, Martino D, Avanzino L, Avenanti A, Vicario CM
Soc Neurosci 2023 Dec;18(6):331-354. Epub 2023 Aug 21 doi: 10.1080/17470919.2023.2248687. PMID: 37580305
Hirsch LE, Pringsheim T
Cochrane Database Syst Rev 2016 Jun 26;2016(6):CD009043. doi: 10.1002/14651858.CD009043.pub3. PMID: 27344135Free PMC Article
Pietracupa S, Bruno E, Cavanna AE, Falla M, Zappia M, Colosimo C
J Neurol Sci 2015 Nov 15;358(1-2):9-21. Epub 2015 Sep 2 doi: 10.1016/j.jns.2015.08.1544. PMID: 26428309
Ching H, Pringsheim T
Cochrane Database Syst Rev 2012 May 16;(5):CD009043. doi: 10.1002/14651858.CD009043.pub2. PMID: 22592735
van Wyk GW, Hazell PL, Kohn MR, Granger RE, Walton RJ
J Atten Disord 2012 May;16(4):314-24. Epub 2011 Feb 2 doi: 10.1177/1087054710389989. PMID: 21289234

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