Format

Send to:

Choose Destination

PEHO syndrome(PEHO)

MedGen UID:
342404
Concept ID:
C1850055
Disease or Syndrome
Synonyms: Infantile cerebellooptic atrophy; PEHO; Progressive Encephalopathy with edema, Hypsarrhythmia, and Optic atrophy
SNOMED CT: Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy syndrome (442511009); PEHO syndrome (442511009); PEHO (progressive encephalopathy with edema, hypsarrhythmia and optic atrophy) syndrome (442511009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): ZNHIT3 (17q12)
 
Monarch Initiative: MONDO:0009841
OMIM®: 260565
Orphanet: ORPHA2836

Definition

PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral edema (summary by Anttonen et al., 2017). [from OMIM]

Clinical features

From HPO
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Sign or Symptom
A rapid, involuntary jerk of a muscle or group of muscles.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
A disorder characterized by loss of optic nerve fibers. It may be inherited or acquired. Acquired causes include ischemia, optic nerve neuropathy, glaucoma, trauma, radiation, brain tumors, and multiple sclerosis. It leads to vision disturbances.
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Autonomic nervous system overreaction to stimuli, most commonly after spinal cord injury at a T-5 level and above.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
A developmental brain abnormality characterized by an excessive amount of small convolutions on the surface of the brain and cognitive dysfunction.
Macrogyria
MedGen UID:
120579
Concept ID:
C0266483
Congenital Abnormality
Increased size of cerebral gyri, often associated with a moderate reduction in the number of sulci of the cerebrum.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
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.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Atrophy (wasting) of the cerebellum.
Severe muscular hypotonia
MedGen UID:
326544
Concept ID:
C1839630
Finding
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Developmental stagnation
MedGen UID:
341348
Concept ID:
C1848980
Finding
A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills.
Undetectable visual evoked potentials
MedGen UID:
376697
Concept ID:
C1850069
Finding
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Finding
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Infantile encephalopathy
MedGen UID:
343542
Concept ID:
C1856408
Finding
Encephalopathy with onset in the infantile period.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Edema of the dorsum of hands
MedGen UID:
752076
Concept ID:
C2732374
Finding
Edema of the dorsum of feet
MedGen UID:
753650
Concept ID:
C2919341
Finding
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Retrognathia
MedGen UID:
488375
Concept ID:
C3494422
Finding
A physical misalignment of the upper (maxilla) and lower (mandibular) jaw bones in which either or both recede relative to the frontal plane of the forehead.
Peripheral dysmyelination
MedGen UID:
871139
Concept ID:
C4025610
Finding
Defective structure and function of myelin sheaths. Dysmyelination is distinguished from demyleination where there is destruction or damage of previously normal myelination.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPEHO syndrome

Recent clinical studies

Etiology

Huisman TA, Klein A, Werner B, Straube T, Boltshauser E
AJNR Am J Neuroradiol 2006 Aug;27(7):1555-8. PMID: 16908579
D'Arrigo S, Grazia BM, Faravelli F, Riva D, Pantaleoni C
J Child Neurol 2005 May;20(5):454-6. doi: 10.1177/08830738050200051801. PMID: 15968934
Riikonen R, Somer M, Turpeinen U
Epilepsia 1999 Nov;40(11):1642-8. doi: 10.1111/j.1528-1157.1999.tb02051.x. PMID: 10565594
Shevell MI, Colangelo P, Treacy E, Polomeno RC, Rosenblatt B
Pediatr Neurol 1996 Nov;15(4):337-9. doi: 10.1016/s0887-8994(96)00161-0. PMID: 8972535
Somer M, Salonen O, Pihko H, Norio R
AJNR Am J Neuroradiol 1993 Jul-Aug;14(4):861-7. PMID: 8352158

Diagnosis

Nevanlinna V, Konovalova S, Ceulemans B, Muona M, Laari A, Hilander T, Gorski K, Valanne L, Anttonen AK, Tyynismaa H, Courage C, Lehesjoki AE
Eur J Med Genet 2020 Mar;63(3):103766. Epub 2019 Sep 16 doi: 10.1016/j.ejmg.2019.103766. PMID: 31536827
Õunap K, Muru K, Õiglane-Shlik E, Ilves P, Pajusalu S, Kuus I, Wojcik MH, Reimand T
Eur J Med Genet 2020 Feb;63(2):103660. Epub 2019 Apr 29 doi: 10.1016/j.ejmg.2019.04.017. PMID: 31048081Free PMC Article
Samanta D, Gokden M
J Clin Neurosci 2019 Mar;61:298-301. Epub 2018 Oct 29 doi: 10.1016/j.jocn.2018.10.091. PMID: 30385166
Gawlinski P, Posmyk R, Gambin T, Sielicka D, Chorazy M, Nowakowska B, Jhangiani SN, Muzny DM, Bekiesinska-Figatowska M, Bal J, Boerwinkle E, Gibbs RA, Lupski JR, Wiszniewski W
Pediatr Neurol 2016 Jul;60:83-7. Epub 2016 Apr 9 doi: 10.1016/j.pediatrneurol.2016.03.011. PMID: 27343026Free PMC Article
Langlois S, Tarailo-Graovac M, Sayson B, Drögemöller B, Swenerton A, Ross CJ, Wasserman WW, van Karnebeek CD
Eur J Hum Genet 2016 Jun;24(6):949-53. Epub 2015 Oct 21 doi: 10.1038/ejhg.2015.217. PMID: 26486474Free PMC Article

Therapy

Riikonen R
Int J Mol Sci 2017 Sep 26;18(10) doi: 10.3390/ijms18102056. PMID: 28954393Free PMC Article
Caraballo RH, Pozo AN, Gomez M, Semprino M
Pediatr Neurol 2011 Apr;44(4):259-64. doi: 10.1016/j.pediatrneurol.2010.11.007. PMID: 21397166

Prognosis

Õunap K, Muru K, Õiglane-Shlik E, Ilves P, Pajusalu S, Kuus I, Wojcik MH, Reimand T
Eur J Med Genet 2020 Feb;63(2):103660. Epub 2019 Apr 29 doi: 10.1016/j.ejmg.2019.04.017. PMID: 31048081Free PMC Article
Huisman TA, Klein A, Werner B, Straube T, Boltshauser E
AJNR Am J Neuroradiol 2006 Aug;27(7):1555-8. PMID: 16908579
D'Arrigo S, Grazia BM, Faravelli F, Riva D, Pantaleoni C
J Child Neurol 2005 May;20(5):454-6. doi: 10.1177/08830738050200051801. PMID: 15968934
Klein A, Schmitt B, Boltshauser E
Eur J Paediatr Neurol 2004;8(6):317-21. doi: 10.1016/j.ejpn.2004.08.006. PMID: 15542387
Shevell MI, Colangelo P, Treacy E, Polomeno RC, Rosenblatt B
Pediatr Neurol 1996 Nov;15(4):337-9. doi: 10.1016/s0887-8994(96)00161-0. PMID: 8972535

Clinical prediction guides

Õunap K, Muru K, Õiglane-Shlik E, Ilves P, Pajusalu S, Kuus I, Wojcik MH, Reimand T
Eur J Med Genet 2020 Feb;63(2):103660. Epub 2019 Apr 29 doi: 10.1016/j.ejmg.2019.04.017. PMID: 31048081Free PMC Article
Caraballo RH, Pozo AN, Gomez M, Semprino M
Pediatr Neurol 2011 Apr;44(4):259-64. doi: 10.1016/j.pediatrneurol.2010.11.007. PMID: 21397166
Fujimoto S, Yokochi K, Nakano M, Wada Y
Neuropediatrics 1995 Oct;26(5):270-2. doi: 10.1055/s-2007-979771. PMID: 8552220
Haltia M, Somer M
Acta Neuropathol 1993;85(3):241-7. doi: 10.1007/BF00227717. PMID: 8460530

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center