title: Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome.
abstract: Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.
authors: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
authors: Saskia B
authors: SB
authors: Wortmann
authors: Department of Metabolic Diseases, Wilhelmina Children's Hospital Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Peter M
authors: PM
authors: van Hasselt
authors: Department of Pediatrics, University Hospital Centre Zagreb and University of Zagreb, School of Medicine, Zagreb, Croatia.
authors: Ivo
authors: I
authors: Barić
authors: Division of Inherited Metabolic Diseases, Department of Pediatrics, University Hospital of Padua, Padua, Italy.
authors: Alberto
authors: A
authors: Burlina
authors: Department of Pediatrics, University of Gothenburg, The Queen Silvia's Children Hospital, Gothenburg, Sweden.
authors: Niklas
authors: N
authors: Darin
authors: Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors: Friederike
authors: F
authors: Hörster
authors: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey.
authors: Mahmut
authors: M
authors: Coker
authors: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey.
authors: Sema Kalkan
authors: SK
authors: Ucar
authors: Medical Genetics Clinic, Children's University Hospital, Riga, Latvia.
authors: Zita
authors: Z
authors: Krumina
authors: Department of Pediatric Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors: Karin
authors: K
authors: Naess
authors: Division of Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors: Lock H
authors: LH
authors: Ngu
authors: Department of Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.
authors: Ewa
authors: E
authors: Pronicka
authors: Department of Pediatric Neurology, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa.
authors: Gilian
authors: G
authors: Riordan
authors: Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Rene
authors: R
authors: Santer
authors: Birmingham Children's Hospital, Birmingham, United Kingdom.
authors: Evangeline
authors: E
authors: Wassmer
authors: Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria.
authors: Johannes
authors: J
authors: Zschocke
authors: Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, INSERM U1141 and Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
authors: Manuel
authors: M
authors: Schiff
authors: Pediatric Neurology and Metabolic Diseases, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors: Linda
authors: L
authors: de Meirleir
authors: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Mohammed A
authors: MA
authors: Alowain
authors: Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
authors: Jan A M
authors: JA
authors: Smeitink
authors: Hayward Genetics Center and Department of Pediatrics, Tulane University Medical School, New Orleans, LA, United States.
authors: Eva
authors: E
authors: Morava
authors: Department of Anatomy, Radboudumc, Nijmegen, The Netherlands.
authors: Tamas
authors: T
authors: Kozicz
authors: Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases (LGEM), Radboudumc, Nijmegen, The Netherlands.
authors: Ron A
authors: RA
authors: Wevers
authors: Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Nicole I
authors: NI
authors: Wolf
authors: Department of Neurology, Radboudumc, Nijmegen, The Netherlands.
authors: Michel A
authors: MA
authors: Willemsen
mesh_terms: D001479:Basal Ganglia / Q000473:pathology*; D002675:Child, Preschool; D003638:Deafness / Q000150:complications / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D020821:Dystonic Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D028361:Mitochondrial Diseases / Q000150:complications / Q000473:pathology*; D011699:Putamen / Q000473:pathology; D013577:Syndrome