title: Clinical and molecular delineation of Tetrasomy 9p syndrome: report of 12 new cases and literature review.
abstract: Tetrasomy 9p is a generic term describing the presence of a supernumerary chromosome incorporating two copies of the 9p arm. Two varieties exist: isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one inactive centromere are linked together by a proximal segment of 9q that may incorporate euchromatic material. In living patients, i(9p) and idic(9p) are usually present in a mosaic state. Fifty-four cases, including fetuses, have been reported, of which only two have been molecularly characterized using array-CGH. Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital anomalies with severe intellectual disability and growth delay to subnormal cognitive and physical developments. Hypertelorism, abnormal ears, microretrognathia and bulbous nose are the most common dysmorphic traits. Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal anomalies were reported in several cases. Those physical anomalies are often, but not universally, accompanied by intellectual disability. The most recurrent breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one structurally uncharacterized), including the first case of parental germline mosaicism. All rearrangements have been characterized by DNA microarray. Based on our results and a review of the literature, we further delineate the prenatal and postnatal clinical spectrum of this imbalance. Our results show poor genotype-phenotype correlations and underline the need of precise molecular characterization of the supernumerary marker.
authors.affiliation: Cochin Institute, INSERM U1016, Paris, France.|Cytogenetics Department, APHP, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Laïla
authors.initials: L
authors.lastname: El Khattabi
authors.affiliation: Cytogenetics and Cell Biology Department, Rennes University Hospital, Rennes, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jaillard
authors.affiliation: Medical Genetics Department, Lille Hospital, Lille, France.
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.affiliation: Medical Genetics Department, Rennes University Hospital, Rennes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Perrin
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital, Paris, France.
authors.forename: Yline
authors.initials: Y
authors.lastname: Capri
authors.affiliation: Pediatrician, Oran, Algeria.
authors.forename: Abdelmadjid
authors.initials: A
authors.lastname: Benmansour
authors.affiliation: Department of Genetics, Tours University Hospital, Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: Department of Pathology, CHU Brest, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.affiliation: Department of Genetics, Arras Hospital, Arras, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vincent-Delorme
authors.affiliation: Department of Medical Genetics, CHBA, Vannes, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.affiliation: Cytogenetics and Cell Biology Department, Rennes University Hospital, Rennes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Henry
authors.affiliation: Department of Pediatrics, Saint-Brieuc Hospital, Saint-Brieuc, France.
authors.forename: Claire
authors.initials: C
authors.lastname: De Barace
authors.affiliation: Department of Anatomy and Cell Pathology, CHRU Lille, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Devisme
authors.affiliation: Molecular Genetics Department, Rennes University Hospital, Rennes, France.|UMR 6290, IGDR, Medical School, Rennes, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.affiliation: Medical Genetics Department, Rennes University Hospital, Rennes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Demurger
authors.affiliation: Cytogenetics and Cell Biology Department, Rennes University Hospital, Rennes, France.
authors.forename: Josette
authors.initials: J
authors.lastname: Lucas
authors.affiliation: Cytogenetics and Cell Biology Department, Rennes University Hospital, Rennes, France.|UMR 6290, IGDR, Medical School, Rennes, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Belaud-Rotureau
authors.affiliation: Department of Genetics, APHP, Necker-Enfants Malades University Hospital, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.affiliation: Laboratory of Cytogenetics, APHP, Necker-Enfants Malades Hospital, Paris Descartes University, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.affiliation: Laboratory of Cytogenetics, APHP, Necker-Enfants Malades Hospital, Paris Descartes University, Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: De Blois
authors.affiliation: Department of Pediatrics, Jean-Verdier Hospital, APHP, Paris 13 University, Bondy, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: De Pontual
authors.affiliation: Cytogenetics Department, APHP, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Aziza
authors.initials: A
authors.lastname: Lebbar
authors.affiliation: Cytogenetics Department, APHP, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Dû
authors.affiliation: Department of Genetics, Raymond Poincaré University Hospital, Garches, France.
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.affiliation: Department of Neuropediatrics, Raymond Poincaré University Hospital, Garches, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Pinard
authors.affiliation: Cytogenetics, APHP, Jean-Verdier University Hospital, Bondy; Paris 13, Sorbonne Paris Cité, UFR SMBH, Bobigny, France; Inserm, U676, Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Pipiras
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital, Paris, France.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Tabet
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital, Paris, France.
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital, Paris, France.|INSERM U676, and Paris VII-Denis Diderot Medical School, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002899:Chromosomes, Human, Pair 9; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D005260:Female; D005333:Fetus; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013577:Syndrome; D014314:Trisomy
keywords: isochromosome; microarray; mosaicism; tetrasomy 9p