Alternative titles; symbols
PROGRESSIVE ENCEPHALOPATHY WITH EDEMA, HYPSARRHYTHMIA, AND OPTIC ATROPHYINFANTILE CEREBELLOOPTIC ATROPHYPEHO-LIKE SYNDROME, INCLUDED
Salonen et al. (1991) identified a new form of infantile progressive encephalopathy in 14 patients, 8 of whom were female, from 11 families. The clinical signs included severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperreflexia, transient or persistent edema, and optic atrophy. Other features included microcephaly and atrophy of the brain, especially in the cerebellar and brain stem areas. Salonen et al. (1991) pictured edema of the hands and tapering of the fingers resembling somewhat the hands in the Coffin-Lowry syndrome (303600). Facial anomalies included a 'pear-shaped' face, protruding lower parts of the earlobes, short nose, and open mouth with curved upper lip. No metabolic abnormality was found.
Haltia and Somer (1993) reported the neuropathologic findings in 8 cases: 3 patients in the original group described by Salonen et al. (1991) and 5 others collected from medical records. Two of the 8 patients were sibs. In addition, 1 patient had 1 sib, and another patient had 2 similarly affected sibs. Macroscopically, cerebral and pronounced cerebellar atrophy was seen, the essential histopathologically lesions being confined to the cerebellar cortex and the optic nerve. There was a severe neuronal loss in the inner granular layer of the cerebellum. The Purkinje cells were relatively preserved in number but were small, deformed, and slightly disaligned. Haltia and Somer (1993) found some similarities to congenital cerebellar granular cell hypoplasia and mental retardation (213200); however, mental retardation was less severe, and no epilepsy or optic atrophy was reported.
In a combined neuroradiologic and ophthalmologic study, Somer (1993) found that 10 of 21 possible patients had the true PEHO syndrome according to clinical criteria suggested by the authors. All were abnormal at birth, showing hypotonia, drowsiness, or poor feeding. Head circumference was normal at birth, but usually dropped to 2 SD below average during the first year of life. Visual fixation was either absent from birth or lost during the first months of life. Nine patients had peripheral edema in early childhood. The mean age of onset of infantile spasms was 4.9 months, no motor milestones were ever reached, and patellar reflexes were brisk. Brain stem and somatosensory evoked potentials were abnormal in each case studied, cortical responses of somatosensory evoked potentials could not be elicited, and motor conduction velocities became delayed with age. A total of 19 PEHO patients were found in 14 Finnish families in a pattern consistent with autosomal recessive inheritance. Somer (1993) indicated that cerebellar hypoplasia is a cardinal diagnostic feature of PEHO syndrome and suggested that a PEHO-like syndrome (the same clinical manifestations with only mild supratentorial atrophy) may occur.
Fujimoto et al. (1995) reported 2 affected sibs, a male and a female, born to healthy parents of Japanese descent who fulfilled the necessary diagnostic criteria for the PEHO syndrome established by Somer (1993) but who lacked supportive criteria of peripheral edema. In the female, there was mild elevation of the plasma lactate level only during the first year of life without an accompanying elevation of lactate in the cerebrospinal fluid.
Chitty et al. (1996) described 2 female sibs and 2 unrelated infants (a boy and a girl) with progressive encephalopathy, seizures, which started between 3 days and 13 months of age, characteristic facies, edema of the hands and feet, tapering fingers, and optic atrophy. All 4 patients died between 10 weeks and 34 months of age. Autopsies were declined. MRI, which was performed in 3 cases, showed delay in myelinization but no cerebellar atrophy. The patients reported by Chitty et al. (1996) fit the criteria of PEHO-like syndrome, but noted that the distinction between PEHO and PEHO-like cases remained unclear.
Longman et al. (2003) described 2 sisters with a PEHO-like syndrome. The firstborn had early epileptic spasms with hypsarrhythmia, visual inattention with optic atrophy, progressive microcephaly, and absence of development. Cranial MRI revealed periventricular white matter changes. Cerebellar hypoplasia, characteristic of true PEHO syndrome, was absent. The MRI changes were interpreted as periventricular leukomalacia due to prenatal ischemia, and a low recurrence risk was suggested. The younger sister was born similarly affected. Longman et al. (2003) noted that the diagnosis of PEHO syndrome is clinical, but cerebellar hypoplasia on neuroimaging is regarded as an additional necessary criterion. A heterogeneous group of PEHO-like patients, who lacked cerebellar hypoplasia but had varying supratentorial abnormalities, had been reported (Somer, 1993; Chitty et al., 1996). The family reported by Longman et al. (2003) was the second report of sibs with a PEHO-like syndrome, and it supported the existence of a distinct, autosomal recessive condition in which neuroimaging abnormalities may be misinterpreted.
Field et al. (2003) noted that few patients fulfilling the diagnostic criteria for PEHO syndrome had been reported outside Finland. Field et al. (2003) reported 5 Australian patients, the first with classic features of PEHO syndrome, and 4 who had a PEHO-like disorder. They suggested that the disorder may be more frequent than would be suggested based on the original diagnostic criteria.
1. Chitty, L. S.; Robb, S.; Berry, C.; Silver, D.; Baraitser, M. :
PEHO or PEHO-like syndrome? Clin. Dysmorph. 5: 143-152, 1996.PubMed ID : 8723564
2. Field, M. J.; Grattan-Smith, P.; Piper, S. M.; Thompson, E. M.; Haan, E. A.; Edwards, M.; James, S.; Wilkinson, I.; Ades, L. C. :
PEHO and PEHO-like syndromes: report of 5 Australian cases. Am. J. Med. Genet. 122A: 6-12, 2003.PubMed ID : 12949965
3. Fujimoto, S.; Yokochi, F.; Nakano, M.; Wada, Y. :
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) in two Japanese siblings. Neuropediatrics 26: 270-272, 1995.PubMed ID : 8552220
4. Haltia, M.; Somer, M. :
Infantile cerebello-optic atrophy: neuropathology of the progressive encephalopathy syndrome with edema, hypsarrhythmia and optic atrophy (the PEHO syndrome). Acta Neuropath. 85: 241-247, 1993.PubMed ID : 8460530
5. Longman, C.; Tolmie, J.; McWilliam, R.; MacLennan, A. :
Cranial magnetic resonance imaging mistakenly suggests prenatal ischaemia in PEHO-like syndrome. Clin. Dysmorph. 12: 133-136, 2003.PubMed ID : 12868478
6. Salonen, R.; Somer, M.; Haltia, M.; Lorentz, M.; Norio, R. :
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome). Clin. Genet. 39: 287-293, 1991.PubMed ID : 2070547
7. Somer, M. :
Diagnostic criteria and genetics of the PEHO syndrome. J. Med. Genet. 30: 932-936, 1993.PubMed ID : 8301648
Victor A. McKusick - updated : 9/25/2003Iosif W. Lurie - updated : 7/26/1996Orest Hurko - updated : 3/9/1996
Victor A. McKusick : 6/4/1991
ckniffin : 5/19/2004tkritzer : 3/19/2004joanna : 3/17/2004carol : 2/18/2004
Diagnostic criteria and genetics of the PEHO syndrome.
Department of Medical Genetics, Vaestoliitto, Finnish Population and Family Welfare Federation, Helsinki.
The PEHO syndrome (progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy) is a recently recognised disorder of unknown biochemical background. Diagnostic features have been found in neuroradiological and neuropathological studies, which show characteristic severe cerebellar atrophy. In combined neuroradiological and ophthalmological studies, 10 out of 21 possible PEHO patients fulfilled the criteria for true PEHO syndrome. All were abnormal at birth showing hypotonia, drowsiness, or poor feeding. Head circumference was normal, but usually dropped to 2 SD below average during the first year of life. Visual fixation was either absent from birth or lost during the first months of life. Nine patients had peripheral oedema in early childhood. The mean age of onset of infantile spasms was 4.9 months. All patients were extremely hypotonic and no motor milestones were reached. Patellar reflexes were brisk. Brain stem and somatosensory evoked potentials were abnormal in each case studied, cortical responses of somatosensory evoked potentials could not be elicited, and motor conduction velocities became delayed with age. Altogether 19 PEHO patients were found in 14 Finnish families. Autosomal recessive inheritance is likely.PMID: 8301648
[PubMed - indexed for MEDLINE]
D I S E A S E : Peho syndrome
autosomal recessive inheritance (Very frequent sign)
cerebellum agenesis/hypoplasia (Very frequent sign)
cerebral cortex atrophy (Very frequent sign)
depressed premaxillary region (Very frequent sign)
e.e.g.abnormality (Very frequent sign)
hypereflexia (Very frequent sign) hypotonia (Very frequent sign)
long/large ear (Very frequent sign)
mental retardation (moderate/severe) (Very frequent sign)
microcephaly (Very frequent sign)
mouth held open (Very frequent sign)
optic disc anomaly/atrophy (Very frequent sign)
seizures ( any type) (Very frequent sign)
short/small nose (Very frequent sign)
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