hypsarrhythmia

PEHO-Like Syndrome

Clinical Characteristics
Ocular Features: 

Poor visual fixation and attention has been noted during the first 6 months of life.  Optic atrophy has been described and epicanthal folds may be present.

Systemic Features: 

General hypotonia with developmental delay and progressive microcephaly are evident in the first 6-12 months of life.  Seizures may be present at birth or within the first month of life.  Edema of the feet, hands, and face are also present at birth.  Cognitive deficits and motor delays are usually evident during infancy.  The central hypotonia may be accompanied by peripheral spasticity.  Kyphoscoliosis often develops.  Other dysmorphic features include micrognathia, narrow forehead, short nose, and open mouth.

Brain imaging reveals coarse pachygyria, polymicrogyria, and dilated ventricles with hypoplastic corpus callosum and pons.  Cerebellar hypoplasia was found in one child. 

Genetics

This presumed autosomal recessive disorder is associated with homozygous mutations in the CCDC88A gene (2p16.1).  Three affected children have been reported in a consanguineous family.

A somewhat similar disorder known as PEHO syndrome (260565) results from homozygous mutations in the ZNHIT3 gene. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

The PEHO syndrome

Riikonen R. The PEHO syndrome. Brain Dev. 2001 Nov;23(7):765-9. Review.

PubMed ID: 
11701291

Encephalopathy Due To Defective Mitochondrial And Peroxisomal Fission 2

Clinical Characteristics
Ocular Features: 

Visual impairment and optic atrophy are usually present.  Visual-evoked potentials may be negative or slowed severely.  Some degree of ophthalmoparesis is often present while frank external ophthalmoplegia can develop in the second year of life.  In one patient aged 7 years, MRI showed increased T2 signals in the optic radiation.

Systemic Features: 

Microcephaly becomes evident in the first year of life and seizures can appear in this period as well.  General developmental delays are present.  There may be evidence of Leigh-like basal ganglia disease.  Dysphagia may require the placement of a gastroscopy tube.  Truncal hypotonia can be so severe that sitting and head control are not possible.  However, there is often spasticity and hyperreflexia in the limbs.  EEG recordings show hypsarrhythmia.

Brain MRI may show increased T2 signaling in the global pallidus, thalamus, and the subthalamic nucleus.

Patients may never be able to sit or walk and usually do not develop speech.  

Genetics

Homozygous or compound heterozygous truncating mutations in the MFF gene (mitochondrial fission factor) (2q36.3) is responsible for this condition.  Patients with EMPF2 may have abnormally elongated and tubular mitochondria and peroxisomes in fibroblasts.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the general disorder.  Gastrostomy tubes may be required to maintain adequate nutrition.  Airway hygiene is important.  Respiratory complications can be a factor in the early demise of children.

References
Article Title: 
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