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Disease Profile

PEHO syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G31.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Progressive Encephalopathy with edema, Hypsarrhythmia, and Optic atrophy; Infantile cerebellooptic atrophy

Categories

Blood Diseases; Congenital and Genetic Diseases; Eye diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 2836

Definition
PEHO (Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy) syndrome is a rare neurodegenerative disorder belonging to the group of infantile progressive encephalopathies.

Epidemiology
The incidence in Finland has been estimated at 1 in 78 000, but a few patients have been described from other countries including (The Netherlands, Spain France).

Clinical description
Onset occurs during the first few weeks or months of life with hypotonia, poor feeding, drowsiness and abnormal movements. Infantile spasms, hypsarrhythmia and seizures appear during the first year of life. Visual loss, abnormal eye movements and optic atrophy also occur during infancy. Other features include early arrest of psychomotor development, severe intellectual deficit, microcephaly, edema (particularly of the extremities), tapered fingers and facial dysmorphism (including a 'Pear-shaped' face with a narrow forehead and full cheeks, receding chin, epicanthic folds, an open mouth with a curved upper lip, protruding ear lobes and a short nose with anteverted nostrils).

Etiology
Transmission appears to be autosomal recessive but the etiology is unknown. The only biochemical anomalies identified so far are elevated levels of nitrite, nitrate and nitric oxide (NO), and low levels of insulin-like growth factor 1 (IGF-1) in the cerebrospinal fluid (CSF).

Diagnostic methods
Diagnosis is mainly clinical and depends on the presence of the following diagnostic criteria: early-onset severe hypotonia; the occurrence of seizures, infantile spasms and hypsarrhythmia after the first two weeks of life; onset of optic atrophy before two years of age, and failure to obtain any of the milestones for motor, visual and language development. An additional criterion is demonstration of cerebellar and brainstem atrophy by MRI. A significant number of patients have been described who displayed most of the diagnostic criteria and features of PEHO syndrome, but did not appear to have cerebral atrophy on MRI, lacked the ophthalmologic signs and showed no reduction in CSF IGF-1 levels. This group of patients was diagnosed with PEHO-like syndrome.

Differential diagnosis
The differential diagnosis should include Aicardi syndrome, mevalonic aciduria, the carbohydrate-deficient glycoprotein (CDG) syndromes, autosomal recessive cerebellar hypoplasia, Joubert syndrome and olivo-pontine cerebellar atrophies (see these terms).

Antenatal diagnosis
Prenatal diagnosis is not available but early diagnosis is essential for genetic counseling of affected families.

Management and treatment
Treatment is symptomatic only. The infantile spasms are refractory to antiepileptic drugs or adrenocorticotropic hormone (ACTH) therapy.

Prognosis
The prognosis is poor and most patients die before 15 years of age, mainly as a result of pneumonia or aspiration.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

0000174
Abnormality of eye movement
Abnormal eye movement
Abnormal eye movements
Eye movement abnormalities
Eye movement issue

[ more ]

0000496
Abnormality of upper lip
0000177
Biparietal narrowing
0004422
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Drowsiness
Sleepy
0002329
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
External ear malformation
0008572
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Global developmental delay
0001263
Hyperreflexia
Increased reflexes
0001347
Hypsarrhythmia
0002521
Infantile spasms
0012469
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Macrotia
Large ears
0000400
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Open mouth
Gaped jawed appearance
Gaped mouthed appearance
Slack jawed appearance

[ more ]

0000194
Optic atrophy
0000648
Severe muscular hypotonia
Severely decreased muscle tone
0006829
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Tapered finger
Tapered fingertips
Tapering fingers

[ more ]

0001182
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
30%-79% of people have these symptoms
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Atrophy/Degeneration affecting the brainstem
0007366
Cerebellar atrophy
Degeneration of cerebellum
0001272
Gingival overgrowth
Gum enlargement
0000212
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Palpebral edema
Fullness of eyelids
Puffy eyelids
Puffy lids
Swelling of eyelids

[ more ]

0100540
Pedal edema
Fluid accumulation in lower limbs
Lower leg swelling

[ more ]

0010741
Peripheral edema
0012398
Porencephalic cyst
Cavity within brain
0002132
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Ventriculomegaly
0002119
5%-29% of people have these symptoms
Arthrogryposis multiplex congenita
0002804
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Developmental stagnation
0007281
Edema of the dorsum of feet
0012098
Edema of the dorsum of hands
0007514
Feeding difficulties in infancy
0008872
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Infantile encephalopathy
0007105
Intellectual disability, profound
IQ less than 20
0002187
Myoclonus
0001336
Narrow forehead
Decreased width of the forehead
0000341
Neuronal loss in central nervous system
Loss of brain cells
0002529
Pachygyria
Fewer and broader ridges in brain
0001302
Peripheral dysmyelination
0003469
Polymicrogyria
More grooves in brain
0002126
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Seizure
0001250
Tented upper lip vermilion

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss PEHO syndrome. Click on the link to view a sample search on this topic.

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