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Hyperekplexia 3(HKPX3)

MedGen UID:
766202
Concept ID:
C3553288
Disease or Syndrome
Synonyms: HKPX3; HYPEREKPLEXIA 3, AUTOSOMAL DOMINANT; HYPEREKPLEXIA 3, AUTOSOMAL RECESSIVE; SLC6A5-Related Hyperekplexia
 
Gene (location): SLC6A5 (11p15.1)
 
Monarch Initiative: MONDO:0013827
OMIM®: 614618

Definition

Hereditary hyperekplexia may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year.

The signs and symptoms of hereditary hyperekplexia typically fade by age 1. However, older individuals with hereditary hyperekplexia may still startle easily and have periods of rigidity, which can cause them to fall down. They may also continue to have hypnagogic myoclonus or movements during sleep. As they get older, individuals with this condition may have a low tolerance for crowded places and loud noises. People with hereditary hyperekplexia who have epilepsy have the seizure disorder throughout their lives.

Other signs and symptoms of hereditary hyperekplexia can include muscle twitches when falling asleep (hypnagogic myoclonus) and movements of the arms or legs while asleep. Some infants, when tapped on the nose, extend their head forward and have spasms of the limb and neck muscles. Rarely, infants with hereditary hyperekplexia experience recurrent seizures (epilepsy).

Hereditary hyperekplexia is a condition in which affected infants have increased muscle tone (hypertonia) and an exaggerated startle reaction to unexpected stimuli, especially loud noises. Following the startle reaction, infants experience a brief period in which they are very rigid and unable to move. During these rigid periods, some infants stop breathing, which, if prolonged, can be fatal. Infants with hereditary hyperekplexia have hypertonia at all times, except when they are sleeping. [from MedlinePlus Genetics]

Clinical features

From HPO
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
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.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
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.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscle stiffness
MedGen UID:
113151
Concept ID:
C0221170
Sign or Symptom
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Hiatus hernia
MedGen UID:
483347
Concept ID:
C3489393
Acquired Abnormality
The presence of a hernia in which the upper part of the stomach, i.e., mainly the gastric cardia protrudes through the diaphragmatic esophageal hiatus.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Respiratory arrest
MedGen UID:
57878
Concept ID:
C0162297
Pathologic Function
Cessation of breathing function.
Meconium stained amniotic fluid
MedGen UID:
604683
Concept ID:
C0426209
Finding
Amniotic fluid containing the earliest stools of a mammalian infant.
Ventouse delivery
MedGen UID:
853319
Concept ID:
C1456852
Finding
Delivery of newborn by means of a ventouse, a vacuum device used to assist the delivery of a baby when the second stage of labor has not progressed adequately.

Professional guidelines

PubMed

Masri A, Chung SK, Rees MI
Brain Dev 2017 Apr;39(4):306-311. Epub 2016 Nov 11 doi: 10.1016/j.braindev.2016.10.010. PMID: 27843043
Thomas RH, Drew CJ, Wood SE, Hammond CL, Chung SK, Rees MI
J Neurol Neurosurg Psychiatry 2015 Mar;86(3):341-3. Epub 2014 Jun 26 doi: 10.1136/jnnp-2014-307903. PMID: 24970905
Dreissen YE, Tijssen MA
Epilepsia 2012 Dec;53 Suppl 7:3-11. doi: 10.1111/j.1528-1167.2012.03709.x. PMID: 23153204

Recent clinical studies

Therapy

Vuilleumier PH, Fritsche R, Schliessbach J, Schmitt B, Arendt-Nielsen L, Zeilhofer HU, Curatolo M
Brain 2018 Jan 1;141(1):63-71. doi: 10.1093/brain/awx289. PMID: 29149236
Mineyko A, Whiting S, Graham GE
Can J Neurol Sci 2011 May;38(3):411-6. doi: 10.1017/s0317167100011793. PMID: 21515498
Hamelin S, Rohr P, Kahane P, Minotti L, Vercueil L
Epileptic Disord 2004 Sep;6(3):169-72. PMID: 15504715
Shahar E, Raviv R
Pediatr Neurol 2004 Jul;31(1):30-4. doi: 10.1016/j.pediatrneurol.2003.12.007. PMID: 15246489
Hayashi T, Tachibana H, Kajii T
Am J Med Genet 1991 Aug 1;40(2):138-43. doi: 10.1002/ajmg.1320400203. PMID: 1897565

Prognosis

Dolu MH, Öz Tunçer G, Akça Ü, Aydın S, Bahadir O, Sezer Ö, Aksoy A, Taşdemir HA
J Child Neurol 2024 Jun;39(7-8):260-267. Epub 2024 Jul 25 doi: 10.1177/08830738241263243. PMID: 39051604
Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282
Masri A, Chung SK, Rees MI
Brain Dev 2017 Apr;39(4):306-311. Epub 2016 Nov 11 doi: 10.1016/j.braindev.2016.10.010. PMID: 27843043
Mineyko A, Whiting S, Graham GE
Can J Neurol Sci 2011 May;38(3):411-6. doi: 10.1017/s0317167100011793. PMID: 21515498
Fejerman N
Indian J Pediatr 1997 Sep-Oct;64(5):583-602. doi: 10.1007/BF02726110. PMID: 10771893

Clinical prediction guides

Carapancea E, Cornet MC, Milh M, De Cosmo L, Huang EJ, Granata T, Striano P, Ceulemans B, Stein A, Morris-Rosendahl D, Conti G, Mitra N, Raymond FL, Rowitch DH, Solazzi R, Vercellino F, De Liso P, D'Onofrio G, Boniver C, Danhaive O, Carkeek K, Salpietro V, Weckhuysen S, Fedrigo M, Angelini A, Castellotti B, Lederer D, Benoit V, Raviglione F, Guerrini R, Dilena R, Cilio MR
Neurology 2023 Mar 21;100(12):e1234-e1247. Epub 2023 Jan 4 doi: 10.1212/WNL.0000000000206755. PMID: 36599696Free PMC Article
Ben Mohamed D, Zouari R, Ketata J, Nabli F, Blel S, Ben Sassi S
Seizure 2023 Jan;104:12-14. Epub 2022 Nov 22 doi: 10.1016/j.seizure.2022.11.010. PMID: 36446232Free PMC Article
Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282
Simard C, Vogrig A, Joubert B, Muñiz-Castrillo S, Picard G, Rogemond V, Ducray F, Berzero G, Psimaras D, Antoine JC, Desestret V, Honnorat J
Neurol Neuroimmunol Neuroinflamm 2020 May;7(3) Epub 2020 Mar 13 doi: 10.1212/NXI.0000000000000699. PMID: 32170042Free PMC Article
Hamelin S, Rohr P, Kahane P, Minotti L, Vercueil L
Epileptic Disord 2004 Sep;6(3):169-72. PMID: 15504715

Recent systematic reviews

Ferraroli E, Perulli M, Veredice C, Contaldo I, Quintiliani M, Ricci M, Venezia I, Citrigno L, Qualtieri A, Spadafora P, Cavalcanti F, Battaglia DI
Pediatr Neurol 2022 Jul;132:45-49. Epub 2022 May 17 doi: 10.1016/j.pediatrneurol.2022.05.002. PMID: 35636282
Simard C, Vogrig A, Joubert B, Muñiz-Castrillo S, Picard G, Rogemond V, Ducray F, Berzero G, Psimaras D, Antoine JC, Desestret V, Honnorat J
Neurol Neuroimmunol Neuroinflamm 2020 May;7(3) Epub 2020 Mar 13 doi: 10.1212/NXI.0000000000000699. PMID: 32170042Free PMC Article

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