General description

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is a rare, autosomal recessive neurodegenerative disorder that mainly affects infants and young children. It is associated with pathogenic variants in the ZNHIT3 gene and is sometimes considered a type of lymphatic dysplasia due to the presence of subcutaneous edema.

Clinically, the syndrome is characterized by severe hypotonia from infancy, often recognized early due to the infant's floppiness. Affected children experience infantile spasms, typically accompanied by hypsarrhythmia on EEG, and these seizures may later evolve into other types. Progressive intellectual disability is common, and developmental milestones in motor, visual, and language domains are generally not achieved. Optic atrophy develops before the age of two, leading to severe visual impairment or blindness, often presenting as an inability to fixate.

Physical features include distinctive facial characteristics such as a narrow forehead, epicanthic folds, a short nose, a receding chin, and a pear-shaped face with full cheeks during infancy. Tapering fingers and persistent or transient facial and limb edema are also noted. Additional symptoms include microcephaly due to progressive brain atrophy, hyperreflexia with signs like ankle clonus and Babinski reflexes, as well as severe feeding difficulties and drowsiness in the neonatal period. Most patients with this syndrome die before reaching adolescence.

References

1. Yiş, Uluç, et al. "Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy and PEHO-like syndrome: Report of two cases." Journal of Pediatric Neurosciences 6.2 (2011): 165-168.