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Hyperekplexia 2(HKPX2)

MedGen UID:
766205
Concept ID:
C3553291
Disease or Syndrome
Synonyms: GLRB-Related Hyperekplexia; HKPX2
 
Gene (location): GLRB (4q32.1)
 
Monarch Initiative: MONDO:0013828
OMIM®: 614619

Definition

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.

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).

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.

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. [from MedlinePlus Genetics]

Clinical features

From HPO
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Glabellar reflex
MedGen UID:
927587
Concept ID:
C4293678
Finding
A type of primitive reflex that is elicited by repetitive tapping on the forehead. Normal subjects usually blink in response to the first several taps, but if blinking persists, the response is abnormal and considered to be a sign of frontal release. Persistent blinking is also known as Myerson's sign.
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
Disease or Syndrome
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.
Increased fetal movement
MedGen UID:
866900
Concept ID:
C4021256
Finding
An abnormal increase in quantity or strength of fetal movements.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.

Professional guidelines

PubMed

Thomas RH, Chung SK, Wood SE, Cushion TD, Drew CJ, Hammond CL, Vanbellinghen JF, Mullins JG, Rees MI
Brain 2013 Oct;136(Pt 10):3085-95. Epub 2013 Sep 11 doi: 10.1093/brain/awt207. PMID: 24030948
Pearl PL
J Inherit Metab Dis 2009 Apr;32(2):204-13. Epub 2009 Feb 24 doi: 10.1007/s10545-009-1045-8. PMID: 19234868
Buckwalter MS, Testa CM, Noebels JL, Camper SA
Genomics 1993 Aug;17(2):279-86. doi: 10.1006/geno.1993.1322. PMID: 8406478

Recent clinical studies

Etiology

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
Hara M, Ariño H, Petit-Pedrol M, Sabater L, Titulaer MJ, Martinez-Hernandez E, Schreurs MW, Rosenfeld MR, Graus F, Dalmau J
Neurology 2017 Apr 4;88(14):1340-1348. Epub 2017 Mar 3 doi: 10.1212/WNL.0000000000003796. PMID: 28258082Free PMC Article
Luat AF, Kamat D, Sivaswamy L
Pediatr Ann 2015 Feb;44(2):e18-23. doi: 10.3928/00904481-20150203-07. PMID: 25658214
Shahar E, Raviv R
Pediatr Neurol 2004 Jul;31(1):30-4. doi: 10.1016/j.pediatrneurol.2003.12.007. PMID: 15246489
Fejerman N
Indian J Pediatr 1997 Sep-Oct;64(5):583-602. doi: 10.1007/BF02726110. PMID: 10771893

Diagnosis

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
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
Luat AF, Kamat D, Sivaswamy L
Pediatr Ann 2015 Feb;44(2):e18-23. doi: 10.3928/00904481-20150203-07. PMID: 25658214
Espay AJ, Chen R
Continuum (Minneap Minn) 2013 Oct;19(5 Movement Disorders):1264-86. doi: 10.1212/01.CON.0000436156.54532.1a. PMID: 24092290
Fejerman N
Indian J Pediatr 1997 Sep-Oct;64(5):583-602. doi: 10.1007/BF02726110. PMID: 10771893

Therapy

Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
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
Hara M, Ariño H, Petit-Pedrol M, Sabater L, Titulaer MJ, Martinez-Hernandez E, Schreurs MW, Rosenfeld MR, Graus F, Dalmau J
Neurology 2017 Apr 4;88(14):1340-1348. Epub 2017 Mar 3 doi: 10.1212/WNL.0000000000003796. PMID: 28258082Free PMC Article
Espay AJ, Chen R
Continuum (Minneap Minn) 2013 Oct;19(5 Movement Disorders):1264-86. doi: 10.1212/01.CON.0000436156.54532.1a. PMID: 24092290
Shahar E, Raviv R
Pediatr Neurol 2004 Jul;31(1):30-4. doi: 10.1016/j.pediatrneurol.2003.12.007. PMID: 15246489

Prognosis

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
Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
Hara M, Ariño H, Petit-Pedrol M, Sabater L, Titulaer MJ, Martinez-Hernandez E, Schreurs MW, Rosenfeld MR, Graus F, Dalmau J
Neurology 2017 Apr 4;88(14):1340-1348. Epub 2017 Mar 3 doi: 10.1212/WNL.0000000000003796. PMID: 28258082Free PMC Article
Shahar E, Raviv R
Pediatr Neurol 2004 Jul;31(1):30-4. doi: 10.1016/j.pediatrneurol.2003.12.007. PMID: 15246489
Fejerman N
Indian J Pediatr 1997 Sep-Oct;64(5):583-602. doi: 10.1007/BF02726110. PMID: 10771893

Clinical prediction guides

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
Gupta J, Badal S, Anand V, Jauhari P, Chakrabarty B, Gulati S
Neurol India 2022 Jan-Feb;70(1):312-314. doi: 10.4103/0028-3886.338670. PMID: 35263902
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
Thomas RH, Chung SK, Wood SE, Cushion TD, Drew CJ, Hammond CL, Vanbellinghen JF, Mullins JG, Rees MI
Brain 2013 Oct;136(Pt 10):3085-95. Epub 2013 Sep 11 doi: 10.1093/brain/awt207. PMID: 24030948

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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