title: 19q13.32 microdeletion syndrome: three new cases.
abstract: A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 microdeletion syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2-3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 microdeletion syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20-23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, and ZNF541. These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32.
authors.affiliation: Medical Genetics Institute, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles CA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Castillo
authors.affiliation: Medical Genetics Institute, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles CA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kramer
authors.affiliation: Greenwood Genetic Center, Greenwood SC, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.affiliation: Thompson Center for Autism and Neurodevelopmental Disorders, Department of Child Health, University of Missouri, Columbia MO, USA.
authors.forename: Judith H
authors.initials: JH
authors.lastname: Miles
authors.affiliation: Greenwood Genetic Center, Greenwood SC, USA.
authors.forename: Barbara R
authors.initials: BR
authors.lastname: DuPont
authors.affiliation: Signature Genomics, Spokane WA, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Medical Genetics Institute, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles CA, USA. Electronic address: john.graham@cshs.org.
authors.forename: John M
authors.initials: JM
authors.lastname: Graham
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D008297:Male
keywords: 19q13.32 microdeletion; ARHGAP35; Copy number variants; Dysmorphic features; Hypoplastic corpus callosum; Intellectual disability; NAPA; NPAS1; SLC8A2; SNP chromosomal microarray