Atypical presentation of Costeff syndrome-severe psychomotor involvement and electrical status epilepticus during slow wave sleep

Highlights

• We describe a girl with an atypical presentation of Costeff syndrome.

• Costeff syndrome may co-occur with epilepsy.

• Costeff syndrome can have variable phenotype despite identical genotype.

• OPA3 mutations should be tested in all cases with core features of Costeff syndrome.

Abstract

Background

Costeff syndrome or OPA3-related 3-methylglutaconic aciduria is an autosomal recessive neurodegenerative disorder characterized by early onset optic atrophy and choreoathetosis with later onset of ataxia and spasticity. Costeff syndrome is prevalent among Iraqi Jews.

Methods

We describe a 5 year old girl from Syrian Jewish origin with an atypical presentation of Costeff syndrome.

Results

The patient presented with asymmetric optic atrophy, severe dystonia and choreoathetosis and global developmental regression at the age of 7 months; no achievement of independent walking and only minimal speech; and appearance of electrical status epilepticus during slow wave sleep in the second year of life with further deterioration. She harbors the classic mutation (c.143-1G > C) in the OPA3 gene.

Conclusion

Costeff syndrome may present in an atypical manner regarding the ethnic origin, clinical manifestations and co-occurrence of epilepsy. Mutations in OPA3 should be evaluated in all cases presenting with the core features of typical Costeff syndrome.

Introduction

Costeff Syndrome or OPA3-related 3-methylglutaconic aciduria or 3-Methylglutaconic aciduria type III is one of the 5 groups of 3-Methylglutaconic aciduria (MGA) which encompasses a heterogeneous group of disorders, coinciding with elevated levels of urinary 3-MGA. Costeff syndrome is characterized by optic atrophy and an extrapyramidal movement disorder presenting in childhood. Optic atrophy is associated with decreased visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Progressive spasticity and cerebellar ataxia are variably seen in affected children and are more common at later stages. The intelligence is usually within the normal range.1, 2, 3

The diagnosis is suggested by elevated urinary excretion of 3-methylglutaconic acid (3-MGA) and confirmed by identification of biallelic OPA3 pathogenic mutations. The syndrome is inherited in an autosomal recessive manner. It is almost exclusively described in Iraqi Jewish descents, which have a single pathogenic variant (c.143-1G > C) in all affected patients.³ This mutation is suspected to cause mitochondrial dysfunction.⁴

Epilepsy with continuous spikes and waves during slow-wave sleep is an age-related epileptic encephalopathy that is characterized by (1) seizures, (2) an electroencephalography (EEG) pattern of electrical status epilepticus during sleep (ESES), and (3) neurocognitive regression. It can represent an atypical evolution of benign epilepsy with centro-temporal spikes (BECTS) or other “benign” focal childhood epilepsies. It also occurs in children with malformations of cortical development, hydrocephalus or thalamic lesions.⁵

We describe a girl with Costeff syndrome who presented in the first year of life with atypical manifestations including early developmental regression followed by epilepsy with CSWS and further behavioral and cognitive deterioration.