1. 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 FISH with 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
20 ring 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
Deletion size (Mb)
FISH
- Ring complete 6/ %
- Ring with deletions 14/ %
- Mosaicism with monosomy 14
CGH
Ring with deletion + duplication 1/ %
UPD (14)
Absent
Parental origin
Maternal 30% Paternal 70%
73 M18: +/+
14q32.3
RP11-73M18
(3 Mb)
EPILEPSY
Mental retardation
Susceptibility to infections
RETINAL ANOMALIES
Behavior disorders
RP11-435F10
(1.5 Mb)
2,5
435F10: +/-
p11.2q32.3
RP11-815P21
(1.2 Mb)
Present
14qter (telomere)
Deleted
Extent and mapping of different deletions
Phenotypic map 6
2.3
1.5 1
0.5
3.4
No of pat 4 15 11 *
Breakpoint in t(10;14) 3
0.65
3.8 2
4.8
7.2 5
4.3 20 8
Deletions within rings
Duplication within rings
Linear deletions
2.5
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