Diapositiva 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
Subjects: 30
Ring 14 Syndrome is a rare genetic condition,
with clinical signs including
-
Genetic Tests
• 20 ring 14
1. RBG-banded chromosomes (100 cells)
11 males/9 females
Aged: 3-36 years
Psychomotor delay
Seizures
Hypotonia
Microcephaly
Retinitis pigmentosa
Characteristic face
2. Locus-specific FISH with probes (total 62)
spanning the entire chromosome 14q
• 9 linear deletions
3. Array-CGH
- BAC array-CGH, 1Mb : 8 patients
- oligonucleotide array-CGH (Agilent) 4x44B,
75Kb: 4 patients
4 males/5 females
Aged: 1-33 years
• 1 t(10;14)(q25.3;q12) balanced translocation
4. Microsatellite segregation analysis
Results
Ring 14: perinatal period
Ring 14: facial characteristics
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
Ring 14 : Physical anomalies
Major malformations absent
Minor skeletal anomalies (scoliosis)
Café-au-lait spots
Retinal anomalies
Acquired microcephaly
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
Distance from
14 q tel
Deletion size (Mb)
Ring 14 : Genetics
FISH
- Ring complete 6/20
73 M18: +/+
 RP11-73M18 (3 Mb)
- Ring with deletions 14/20
- Mosaicism with monosomy 14
EPILEPSY
•
14q32.3
• Mental retardation
• Susceptibility to infections
p11.2q32.3
• RETINAL ANOMALIES
 RP11-435F10 (1.5 Mb)
CGH
Ring with deletion + duplication 1/12
2,5
435F10: +/-
UPD (14)
Absent
RP11-815P21 (1.2 Mb)
• Behavior disorders
Parental origin
Maternal 30% Paternal 70%
Present
14qter (telomere)
Deleted
Extent and mapping of different deletions
Phenotypic map
Ring 14
1
6
7.2
1
Breakpoint in t(10;14)
1
1
20 15
2.3 1.5 0.5 0.65
No of pat
6
1
6
3
3.8
2.5
4.3
5
Linear 14q deletions
Proximal
*
4
11
8
4.8
Distal
Seizures
++
+
MR
++
+
Visual impairment
+
+
Susceptibilty to infections
+
+
Behavior disorders
+
+
Scoliosis
+
+
Acquired microcephaly
+
+
+
3.4
1
1
Deletions within rings
1
1
1
1
1
1
30 %
70 %
2
Linear deletions
Duplication within rings
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
Genes
Visual impairment
Epilepsy
Microcephaly
MR (+/-)
Brain abnormalities
Infections susceptibility
MR (+)
Behavior disorders
Scoliosis
14q11.2q12
14q32
NRL
RPGRIP1
FOXG1
IGH
8 %