title: A further case of brain-lung-thyroid syndrome with deletion proximal to NKX2-1.
abstract: Brain-lung-thyroid syndrome (OMIM #610978) is associated with mutations in the NK2 homeobox 1 (NKX2-1) gene, a transcription factor important in development. 50% of patients are affected by the full triad, comprising congenital hypothyroidism, benign hereditary chorea and infant respiratory distress syndrome. Four cases have previously been reported where a patient has features consistent with brain-lung-thyroid syndrome and a chromosome 14q13 deletion adjacent to, but not disrupting, NKX2-1. We present a patient who has a phenotype consistent with brain-lung-thyroid syndrome, featuring congenital hypothyroidism and choreoathetoid movements with gross motor delay. Thyroid ultrasound showed a small-normal gland and spontaneous resolution of hypothyroidism. Array CGH revealed a de novo 14q13.2-3 deletion adjacent to but not directly involving NKX2-1. Sequencing of NKX2-1 was normal. This report highlights a further case of chromosomal deletion adjacent to NXK2-1 in a patient with a phenotype consistent with brain-lung-thyroid syndrome, and confirms that array-CGH is a useful test in the investigation of congenital hypothyroidism. Deletion of the adjacent gene MBIP in most reported cases so far may be relevant to the pathogenesis of brain-lung-thyroid syndrome. Deletion of nearby promoter or enhancer elements acting on NKX2-1 could also be an important factor. However, further work is needed to elucidate the pathogenesis of the brain-lung-thyroid phenotype in such cases.
authors.affiliation: West of Scotland Department of Clinical Genetics, Level 2A Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, UK. Electronic address: mira.kharbanda@nhs.net.
authors.forename: Mira
authors.initials: M
authors.lastname: Kharbanda
authors.affiliation: Children's Hospital, University of Mainz, Mainz, Germany. Electronic address: pia.hermanns@unimedizin-mainz.de.
authors.forename: Pia
authors.initials: P
authors.lastname: Hermanns
authors.affiliation: Royal Hospital for Children, Glasgow, UK. Electronic address: Jeremy.Jones@glasgow.ac.uk.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.affiliation: Children's Hospital, University of Mainz, Mainz, Germany. Electronic address: pohlenz@uni-mainz.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Pohlenz
authors.affiliation: Royal Hospital for Children, Glasgow, UK. Electronic address: Iain.Horrocks@ggc.scot.nhs.uk.
authors.forename: Iain
authors.initials: I
authors.lastname: Horrocks
authors.affiliation: Royal Hospital for Children, Glasgow, UK. Electronic address: Malcolm.Donaldson@glasgow.ac.uk.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Donaldson
mesh_terms: D001264:Athetosis / Q000235:genetics*; D002648:Child; D002819:Chorea / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: Array-CGH; Brain-lung-thyroid syndrome; Congenital hypothyroidism; NKX2-1