title: Progressive brain atrophy in Schinzel-Giedion syndrome with a SETBP1 mutation.
abstract: Schinzel-Giedion syndrome is a rare congenital malformation syndrome. Recently, SETBP1 was identified as the causative gene. Herein, we present a Japanese boy with Schinzel-Giedion syndrome resulting from a novel mutation in SETBP1 in order to establish the clinical features and serial MRI findings associated with the syndrome. On the third day of life, the boy was referred to our hospital because of facial abnormalities and feeding difficulty. Midfacial retraction, frontal bossing, deep groove under the eyes, upturned nose, low-set ears, bilateral cryptorchidism, and generalized hypertrichosis were identified on admission. At the age of 7 months, epileptic spasms in series occurred. Based on characteristic facial and skeletal abnormalities and severe developmental delay, we clinically diagnosed him with Schinzel-Giedion syndrome. Direct sequencing of the SETBP1 gene revealed a heterozygous mutation (p.Ile871Ser) in exon 4. Although neither cardiac defect nor choanal stenosis were present in our case, the phenotype of our case was nearly identical to those of previously reported cases confirmed by genetic analysis. Serial MRI from the age of 1 month-3 years revealed progressive brain atrophy, especially in the white matter and basal ganglia. However, myelination was age-appropriate and no obvious abnormal signals in the white matter were seen. Diffusion weighted imaging revealed no abnormal findings. Accumulation of MRI data including diffusion weighted imaging from Schinzel-Giedion syndrome cases is needed to understand the mechanism underlying progressive brain atrophy in this syndrome.
authors.affiliation: Department of Neonatology, Okayama Medical Center, National Hospital Organization, Okayama, Japan. Electronic address: gmd18025@s.okayama-u.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Fujinaga
authors.affiliation: Department of Neonatology, Okayama Medical Center, National Hospital Organization, Okayama, Japan.
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Shimizu
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Medical Genetics, Kurashiki Central Hospital, Kurashiki, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ninomiya
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takanashi
authors.affiliation: Department of Pediatrics, Okayama Medical Center, National Hospital Organization, Okayama, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001284:Atrophy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005091:Exons; D015870:Gene Expression; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D009264:Nails, Malformed / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human
keywords: Brain atrophy; Diffusion weighted imaging; Magnetic resonance imaging; SETBP1; Schinzel-Giedion syndrome