title: Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal neuropathy.
abstract: Goldberg-Shprintzen megacolon syndrome (GOSHS) (OMIM 609460) is characterized by a combination of learning difficulties, characteristic dysmorphic features and Hirschsprung's disease. Variable clinical features include iris coloboma, congenital heart defects and central nervous system abnormalities, in particular polymicrogyria. GOSHS has been attributed to recessive mutations in KIAA1279, encoding kinesin family member (KIF)-binding protein (KBP) with a crucial role in neuronal microtubule dynamics. Here we report on a 7-year-old girl with GOSHS as a result of a homozygous deletion of exons 5 and 6 of the KIAA1279 gene. She had been referred with the suspicion of an underlying neuromuscular disorder before the genetic diagnosis was established, prompted by the findings of motor developmental delay, hypotonia, ptosis and absent reflexes. Neurophysiological studies revealed unequivocal evidence of a peripheral axonal sensory motor neuropathy. We hypothesize that an axonal sensory motor neuropathy may be part of the phenotypical spectrum of KIAA1279-related GOSHS, probably reflecting the effects of reduced KBP protein expression on peripheral neuronal function.
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Hormos Salimi
authors.initials: HS
authors.lastname: Dafsari
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.affiliation: Department of Neurophysiology, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pitt
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Jan Dh
authors.initials: JD
authors.lastname: Jongbloed
authors.affiliation: Department of Clinical Genetics, Guy's Hospital, London, UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Flinter
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.|Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK.|Department of Basic and Clinical Neuroscience, IoPPN, King's College, London, UK.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: D001483:Base Sequence; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D015870:Gene Expression; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
chemical_list: C503132:KIFBP protein, human; D009419:Nerve Tissue Proteins
keywords: Goldberg-Shprintzen megacolon syndrome (GOSHS); KIAA1279 gene; neurocristopathies; sensory motor axonal neuropathy