Silver-Russell syndrome: genetic basis and molecular genetic testing
<p>Abstract</p> <p>Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs) are clinically characteri...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Online Access: | http://www.ojrd.com/content/5/1/19 |
| _version_ | 1818528766179147776 |
|---|---|
| author | Binder Gerhard Begemann Matthias Eggermann Thomas Spengler Sabrina |
| author_facet | Binder Gerhard Begemann Matthias Eggermann Thomas Spengler Sabrina |
| author_sort | Binder Gerhard |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs) are clinically characterised by growth disturbances. A noteable imprinting disorder is Silver-Russell syndrome (SRS), a congenital disease characterised by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry and further less characteristic features. However, the clinical spectrum is broad and the clinical diagnosis often subjective. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical SRS features. Nearly one tenth of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. More than 1% of patients show (sub)microscopic chromosomal aberrations. Interestingly, in ~7% of 11p15 hypomethylation carriers, demethylation of other imprinted loci can be detected. Clinically, these patients do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. However, an unambiguous (epi)genotype-phenotype correlation can not be delineated.</p> <p>We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7)mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease.</p> |
| first_indexed | 2024-12-11T06:54:16Z |
| format | Article |
| id | doaj.art-42f6d249d9d74d6db8d25cfd25f7ffca |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-11T06:54:16Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-42f6d249d9d74d6db8d25cfd25f7ffca2022-12-22T01:16:48ZengBMCOrphanet Journal of Rare Diseases1750-11722010-06-01511910.1186/1750-1172-5-19Silver-Russell syndrome: genetic basis and molecular genetic testingBinder GerhardBegemann MatthiasEggermann ThomasSpengler Sabrina<p>Abstract</p> <p>Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs) are clinically characterised by growth disturbances. A noteable imprinting disorder is Silver-Russell syndrome (SRS), a congenital disease characterised by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry and further less characteristic features. However, the clinical spectrum is broad and the clinical diagnosis often subjective. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical SRS features. Nearly one tenth of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. More than 1% of patients show (sub)microscopic chromosomal aberrations. Interestingly, in ~7% of 11p15 hypomethylation carriers, demethylation of other imprinted loci can be detected. Clinically, these patients do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. However, an unambiguous (epi)genotype-phenotype correlation can not be delineated.</p> <p>We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7)mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease.</p>http://www.ojrd.com/content/5/1/19 |
| spellingShingle | Binder Gerhard Begemann Matthias Eggermann Thomas Spengler Sabrina Silver-Russell syndrome: genetic basis and molecular genetic testing Orphanet Journal of Rare Diseases |
| title | Silver-Russell syndrome: genetic basis and molecular genetic testing |
| title_full | Silver-Russell syndrome: genetic basis and molecular genetic testing |
| title_fullStr | Silver-Russell syndrome: genetic basis and molecular genetic testing |
| title_full_unstemmed | Silver-Russell syndrome: genetic basis and molecular genetic testing |
| title_short | Silver-Russell syndrome: genetic basis and molecular genetic testing |
| title_sort | silver russell syndrome genetic basis and molecular genetic testing |
| url | http://www.ojrd.com/content/5/1/19 |
| work_keys_str_mv | AT bindergerhard silverrussellsyndromegeneticbasisandmoleculargenetictesting AT begemannmatthias silverrussellsyndromegeneticbasisandmoleculargenetictesting AT eggermannthomas silverrussellsyndromegeneticbasisandmoleculargenetictesting AT spenglersabrina silverrussellsyndromegeneticbasisandmoleculargenetictesting |