American Journal of Medical Genetics 122A:6–12 (2003) PEHO and PEHO-Like Syndromes: Report of Five Australian Cases M.J. Field, 1 * P. Grattan-Smith, 2 S.M. Piper, 1,2 E.M. Thompson, 3 E.A. Haan, 3 M. Edwards, 4,5 S. James, 6 I. Wilkinson, 7 and L.C. Ade `s 1,8 1 Department of Clinical Genetics, The Children’s Hospital at Westmead, New South Wales, Australia 2 Department of Paediatric Neurology, The Children’s Hospital at Westmead, New South Wales, Australia 3 South Australian Clinical Genetics Service, The Women’s and Children’s Hospital, North Adelaide, South Australia, Australia 4 Hunter Genetics, Newcastle, New South Wales, Australia 5 University of Newcastle, Faculty of Medicine and Health Sciences, Newcastle, New South Wales, Australia 6 Centre for Perinatal Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia 7 Department of Paediatric Neurology, The John Hunter Hospital, Newcastle, New South Wales, Australia 8 University of Sydney, Department of Paediatrics and Child Health, Sydney, New South Wales, Australia PEHO syndrome is a rare progressive in- fantile encephalopathy with onset within the first few months of life. Few pa- tients fulfilling the diagnostic criteria for PEHO syndrome have been reported outside Finland. Affected infants have facial dys- morphism and suffer from severe hypotonia, profound mental retardation, convulsions (often with a hypsarrhythmic EEG pattern), transient or persistent peripheral oedema, and optic atrophy. Cerebellar and brainstem atrophy are usually present on neuroima- ging. A PEHO-like syndrome has been de- scribed, in which the affected individuals have neither optic atrophy nor the typical neuroradiological findings. We report five Australian patients, the first with classical features of PEHO syndrome, and four who have a PEHO-like disorder. We compare their features with other published cases. We suggest that PEHO or a PEHO-like syn- drome may affect more patients than are currently identified, based on the original diagnostic criteria for this disorder. ß 2003 Wiley-Liss, Inc. KEY WORDS: hypsarrhythmia; progres- sive encephalopathy; oed- ema; optic atrophy INTRODUCTION The PEHO syndrome (progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy) is a rare progressive infantile encephalopathy, with prob- able autosomal recessive inheritance. The first report of this condition [Salonen et al., 1991] described a group of Finnish patients with a distinctive infantile encephalo- pathy characterized by early hypotonia, developmental regression and seizures by the third month of life. The seizures were often initially myoclonic, and evolved into classical infantile spasms, which were resistant to medical therapy. Hypsarrhythmia was usually evident on the EEG by 1 year of age. There was early de- terioration of visual acuity and optic atrophy was typically evident by 2 years of age [Salonen et al., 1991; Somer, 1993; Somer and Sainio, 1993]. The infants had growth failure, evolving microcephaly, facial dys- morphism, and characteristic, but unexplained periph- eral oedema. The diagnostic criteria for this disorder were refined by Somer [1993], with patients being classified as having PEHO or a PEHO-like condition (Table I). The PEHO group had all the above features, together with cerebellar and brainstem atrophy by 3 years of age [Somer, 1993; Somer et al., 1993]. PEHO syndrome represents a rare cause of infantile encepha- lopathy. No specific biochemical abnormalities have been identified in this disorder [Riikonen et al., 1999; Vanhatalo and Riikonen, 2000]. It is an important diagnosis because of its genetic implications. The diagnosis should be considered as a cause of infantile spasms, especially where there is a sibling recurrence [Dulac et al., 1993; Somer and Sainio, 1993]. Most of the patients described with PEHO syndrome have been from Finland. A few patients with PEHO or a PEHO-like syndrome are from non-Finnish back- grounds including Japan [Fujimoto et al., 1995], North America [Shevell et al., 1996], and Great Britain [Chitty et al., 1996]. We describe five Australian children, the *Correspondence to: Dr. M.J. Field, M.B.Ch.B., FRACP, Department of Clinical Genetics, Sydney Children’s Hospital, High St, Randwick, NSW 2031, Australia. E-mail: mfield@ivf.com.au Received 25 July 2001; Accepted 12 March 2003 DOI 10.1002/ajmg.a.20216 ß 2003 Wiley-Liss, Inc.