PEHO syndrome

PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia, and Optic atrophy) is a rare, severe neurodegenerative disorder first described in Finnish families. The acronym captures its cardinal features: progressive encephalopathy (brain dysfunction), subcutaneous edema (particularly of the limbs and face), hypsarrhythmia (a severely abnormal electroencephalographic pattern associated with infantile spasms), and optic atrophy (degeneration of the optic nerves leading to visual impairment or blindness). The condition is caused by biallelic pathogenic variants in the ZNHIT3 gene on chromosome 17q25.1, which encodes a protein involved in small nucleolar ribonucleoprotein (snoRNP) assembly and is essential for normal brain development. Affected infants typically appear normal at birth but develop hypotonia (reduced muscle tone), feeding difficulties, and seizures — often infantile spasms with hypsarrhythmia — within the first weeks to months of life. Progressive cerebellar and cerebral atrophy is evident on brain MRI, and psychomotor development is severely impaired, with most children never achieving independent sitting or purposeful hand use. Dysmorphic features may include a narrow forehead, epicanthal folds, short nose, and open mouth. Peripheral edema of the dorsum of the hands and feet, as well as facial puffiness, is a characteristic finding. Optic atrophy develops during infancy, contributing to severe visual impairment. There is currently no curative treatment for PEHO syndrome. Management is supportive and symptomatic, focusing on seizure control with antiepileptic medications (though seizures are often refractory), nutritional support (frequently requiring gastrostomy tube feeding), physical therapy, and management of respiratory complications. Life expectancy is significantly reduced, though some individuals survive into their teens or beyond with intensive supportive care. The condition is most prevalent in Finland but has been reported worldwide.

Common questions about PEHO syndrome