Clinical and molecular delineation of Tetrasomy 9p syndrome: Report of 12 new cases and literature review

Laïla El Khattabi (1, 2) , Sylvie Jaillard (3, 4) , Joris Andrieux (5) , Laurent Pasquier (6) , Laurence Perrin (7) , Yline Capri (7) , Abdelmadjid Benmansour (8) , Annick Toutain (9) , Pascale Marcorelles (10) , Catherine Vincent-Delorme (11) , Hubert Journel (12) , Catherine Henry (4) , Claire de Barace (13) , Louise Devisme (14) , Christèle Dubourg (3, 15) , Florence Demurger (4) , Josette Lucas (4) , Marc-Antoine Belaud-Rotureau (3, 4) , Jeanne Amiel (16) , Valérie Malan (16) , Marie-Christine de Blois (17) , Loïc de Pontual (18) , Aziza Lebbar (2) , Nathalie Le Dû (2) , Dominique P. Germain (19) , Jean-Marc Pinard (20) , Eva Pipiras (21) , Anne-Claude Tabet (7) , Azzedine Aboura (7) , Alain Verloes (22, 7)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 Hôpital Cochin [AP-HP]
3 IGDR - Institut de Génétique et Développement de Rennes
4 Service de Cytogénétique et de Biologie Cellulaire
5 Laboratoire de Génétique Clinique
6 CHU Pontchaillou [Rennes]
7 Département de génétique
8 Chercheur indépendant
9 Service de génétique [Tours]
10 Service d'Anatomie Pathologique
11 Centre de Maladies Rares
12 Génétique Médicale
13 CHU de Saint-Brieuc
14 Pôle de Pathologie, Centre de Biologie Pathologie
15 Service de biologie moléculaire
16 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
17 CHU Necker - Enfants Malades [AP-HP]
18 Hôpital Jean Verdier [AP-HP]
19 Hôpital Raymond Poincaré [AP-HP]
20 Service de neurologie pédiatrique
21 Service Histologie-embryologie-cytogénétique
22 Physiopathologie et neuroprotection des atteintes du cerveau en développement

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. © 2015 Wiley Periodicals, Inc

Keywords: isochromosome; microarray; mosaicism; tetrasomy 9p

Domains: Life Sciences [q-bio]

Laïla El Khattabi, Sylvie Jaillard, Joris Andrieux, Laurent Pasquier, Laurence Perrin, et al.. Clinical and molecular delineation of Tetrasomy 9p syndrome: Report of 12 new cases and literature review. American Journal of Medical Genetics Part A, 2015, 167 (6), pp.1252--1261. ⟨10.1002/ajmg.a.36932⟩. ⟨hal-01165441⟩