PEHO syndrome: well described but easily missed

Aims: PEHO syndrome (progressive encephalopathy, edema, hypsarrhythmia and optic atrophy) is a rare, probably underdiagnosed, neurodegenerative disorder of unknown etiology with autosomal-recessive inheritance (OMIM 260565). In 1991 the syndrome was identified by Salonen in 14 Finnish patients. Since then additional cases have been reported in Australia, Japan, Canada, Spain, Holland and Switzerland. In the absence of genetic and metabolic markers diagnosis relies on clinical criteria defined by Somer in 1993: 1. Early onset of profound muscular hypotonia. 2. Epilepsy with myoclonic seizures, infantile spasms and hypsarrhythmia. 3. Early arrest of psychomotor development. 4. Optic atrophy and absence of visual fixation by two years of age. 5. Progressive cerebellar atrophy.

Case report: The female patient is the second child of non-consanguinous parents of Swiss-German origin. She was born at term after an uneventful pregnancy. During the first weeks of life muscular hypotonia associated with feeding problems was evident. At the age of 5 months frequent infantile spasms and myoclonic seizures ocurred that were refractory to treatment. EEG demonstrated hypsarrhythmia. During the first year of life the girl developed a secondary microcephaly. No milestones for motor, visual and language development were reached. Optic discs were pale and VEPs absent.

Karyotype and neurometabolic investigations were normal. The first cerebral MRI at the age of 5 months was normal. The second MRI at the age of 24 months demonstrated severe cerebellar atrophy, mild supratentorial brain atrophy, delay in myelination and optic atrophy. PEHO syndrome was diagnosed according to the criteria of Somer.

Conclusion: In early onset epileptic encephalopathy with lack of psychomotor development PEHO syndrome should be suspected and MRI repeated. Dysmorphic features and edema are not consistent findings. In view of increasing reports of PEHO syndrome it seems likely that 1. PEHO syndrome is an underdiagnosed neurodegenerative disorder and 2. not confined to Finnish heritage. Early diagnosis is crucial for genetic counseling of affected families.