Case studyAtypical presentation of Costeff syndrome-severe psychomotor involvement and electrical status epilepticus during slow wave sleep
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.
Section snippets
Case study
The patient is the 5 year old daughter of healthy parents from consanguineous, Jewish Syrian origin. She has 2 healthy brothers and no family history of neurological diseases. She was born in Argentina after an uneventful pregnancy. Perinatal history and development until the age of 7 months were described as normal.
At the age of 7 months she developed extrapyramidal movements including dystonia and chorea and gradually lost developmental milestones: the ability to reach out for toys, clapping
Discussion
We describe a child with an atypical presentation of Costeff syndrome regarding ethnicity, laboratory results, clinical manifestations and natural history.
Costeff syndrome is known almost exclusively in Iraqi Jews and the patient we describe is the daughter of consanguineous Syrian Jews. Nevertheless, she harbors the typical Iraqi Jewish mutation of OPA3: c.143-1G > C. After identification of the common Iraqi mutation the family acknowledged the possibility of a distant ancestor migrating from
Conclusion
Our report emphasizes that Costeff syndrome may present in an atypical manner regarding the ethnic origin, metabolic tests, clinical manifestations, natural history and co-occurrence of epilepsy. Mutations in OPA3 should be evaluated in all cases presenting with the core features of Costeff syndrome: optic atrophy and an extrapyramidal movement disorder.
Conflict of interest
None declared.
References (5)
- et al.
Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews
Am J Hum Genet
(2001) - et al.
Two novel compound heterozygous mutations in OPA3 in two siblings with OPA3-related 3-methylglutaconic aciduria
Mol Genet Metab Rep
(2014)
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