THE RING 14 SYNDROME: CLINICAL AND MOLECULAR DEFINITION OF A RARE CONDITION

1. 435F10: +/- 14q32.3 4 6 7.2 Breakpoint in t(10;14) 1 * 1 1 1 20 15 11 8 5 4.3 4.8 3.8 2.5 2.3 1.5 0.5 0.65 3.4 No of pat 1 1 1 1 6 1 1 1 2 6 3 1 1 Deletions within rings Duplication within rings Linear deletions THE RING 14 SYNDROME: CLINICAL AND MOLECULAR DEFINITION OF A RARE CONDITION Giovanni Neri, MD1, Laura Seminara, PhD1, Daniela Orteschi, PhD1, Giuseppe Gobbi, MD2, Simona Giovannini, MD2, Elvio Della Giustina, MD3, Angela Scarano, MD3, Marcella Zollino, MD1 1Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma; 2Neuropsichiatria Infantile, Ospedale Maggiore, Bologna; 3Neuropsichiatria Infantile, Arcispedale S. Maria Nuova, Reggio Emilia, Italy Materials and methods Introduction • Genetic Tests 1. RBG-banded chromosomes (100 cells) • 2. Locus-specific FISHwith probes (total 62) spanning the entire chromosome 14q • 3. Array-CGH • - BAC array-CGH, 1Mb : 8 patients • oligonucleotide array-CGH (Agilent) 4x44B, 75Kb: 4 patients • 4. Microsatellite segregation analysis • Subjects: 30 • 20ring 14 • 11 males/9 females • Aged: 3-36 years • 9 linear deletions • 4 males/5 females • Aged: 1-33 years • 1 t(10;14)(q25.3;q12) balanced translocation Ring 14 Syndrome is a rare genetic condition, with clinical signs including - Psychomotor delay - Seizures - Hypotonia - Microcephaly - Retinitis pigmentosa - Characteristic face Results Ring 14: perinatal period Ring 14: facial characteristics Ring 14 : Physical anomalies Major malformations absent Minor skeletal anomalies (scoliosis) Café-au-lait spots Retinal anomalies Acquired microcephaly Pregnancy - uneventful IUGR uncommon Delivery- at term - normal caesarean section uncommon Birth - normal weight low BW in large 14q deletions - normal length - head circumference: normal, microcephaly possible High forehead Linear eyebrows Hypolastic sopraorbital ridges Deep set eyes Short palpebral fissures/ hypotelorism High nasal bridge Long/asymmetric face Full cheeks Small downturned mouth corners Ear anomalies Ring 14 : Neuropsychology and behavior Hypotonia Seizures Mental retardation Good natured behavior, with hyperactivity and occasional aggressiveness Ring 14 : relevant clinical signs Ring 14 : Genetics Distance from 14 q tel FISH Deletion size (Mb) - Ring complete 6/20 30 % - Ring with deletions 14/20 70 % - Mosaicism with monosomy 14 CGH Ring with deletion + duplication 1/12 8 % UPD (14) Absent Parental origin Maternal 30% Paternal 70% 73 M18: +/+ • RP11-73M18 (3 Mb) • EPILEPSY • Mental retardation • Susceptibility to infections • RETINAL ANOMALIES • Behavior disorders • RP11-435F10 (1.5 Mb) 2,5 p11.2q32.3 • RP11-815P21 (1.2 Mb) Present • 14qter (telomere) Deleted Extent and mapping of different deletions Phenotypic map Ring 14 Linear 14q deletions Proximal Distal Seizures++ + MR ++ + + Visual impairment + + Susceptibilty to infections + + Behavior disorders + + Scoliosis + + Acquired microcephaly + + Genes Visual impairment Epilepsy Microcephaly MR (+/-) Brain abnormalities NRL RPGRIP1 FOXG1 14q11.2q12 Infections susceptibility MR (+) Behavior disorders Scoliosis IGH 14q32 ACKNOWLEDGEMENTS We gratefully acknowledge the financial support of the “Associazione Ring 14” We also thank the patients with the families for participating in this study