BCAP31-associated encephalopathy and complex movement disorder mimicking mitochondrial encephalopathy.
BCAP31, encoded by BCAP31, is involved in the export of transmembrane proteins from the endoplasmic reticulum. Pathogenic variants in BCAP31 results in global developmental delay, dystonia, deafness and dysmorphic features in males, called deafness, dystonia, and cerebral hypomyelination (DDCH) syndrome. We report a new patient with BCAP3-associated encephalopathy, DDCH syndrome, sensorineural hearing loss, generalized dystonia, and choreoathetosis. This 3.5-year-old boy had microcephaly and failure to thrive within the first 3 months of life. His brain MRI showed bilateral increased signal intensity in globus pallidus at age 3 months raising the suspicion of mitochondrial encephalopathy. His muscle biopsy revealed pleomorphic subsarcolemmal mitochondria collection in electron microscopy. Respiratory chain enzyme activities were normal in muscle. He was enrolled to a whole exome sequencing research study, which identified a hemizygous likely pathogenic truncating variant (c.533_536dup; p.Ser180AlafsX6) in BCAP31, inherited from his mother, who had sensorineural hearing loss and normal cognitive functions. We report a new patient with BCAP31-associated encephalopathy, DDCH syndrome, mimicking mitochondrial encephalopathy. We also report a heterozygous mother who has bilateral sensorineural hearing loss. This patient's clinical features, muscle histopathology, brain MRI features, and family history were suggestive of mitochondrial encephalopathy. Whole exome sequencing research study confirmed the diagnosis of BCAP31-associated encephalopathy, DDCH syndrome.
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Saleh
S
Albanyan
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Amal
A
Al Teneiji
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Nasim
N
Monfared
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.|Genetics and Genome Biology Research Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Saadet
http://orcid.org/0000-0001-8396-6764
S
Mercimek-Mahmutoglu
D002675:Child, Preschool; D006319:Hearing Loss, Sensorineural / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017237:Mitochondrial Encephalomyopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D009069:Movement Disorders / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation
C091247:BCAP31 protein, human; D008565:Membrane Proteins
BCAP31; deafness; dystonia and cerebral hypomyelination syndrome sensorineural hearing loss; encephalopathy; mitochondrial encephalopathy; movement disorder