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PEHO (Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy) syndrome is a rare neurodegenerative disorder belonging to the group of infantile progressive encephalopathies.
ORPHA:2836Classification level: Disorder
- Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy
- Progressive encephalopathy-optic atrophy syndrome
- Prevalence: Unknown
- Inheritance: Autosomal dominant or Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: G31.8
- OMIM: 260565
- UMLS: C0796122 C1850055
- MeSH: C536317
- GARD: 4264
- MedDRA: -
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).
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).
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).
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.
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).
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.
The prognosis is poor and most patients die before 15 years of age, mainly as a result of pneumonia or aspiration.