Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum
The amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1198821/full |
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| author | Alessandro Vimercati Pierpaola Tannorella Eleonora Orlandini Luciano Calzari Mirella Moro Sara Guzzetti Angelo Selicorni Milena Crippa Lidia Larizza Maria Teresa Bonati Silvia Russo |
| author_facet | Alessandro Vimercati Pierpaola Tannorella Eleonora Orlandini Luciano Calzari Mirella Moro Sara Guzzetti Angelo Selicorni Milena Crippa Lidia Larizza Maria Teresa Bonati Silvia Russo |
| author_sort | Alessandro Vimercati |
| collection | DOAJ |
| description | The amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) or Gain-of-Methyaltion (GoM) causes Silver–Russell syndrome (SRS) or Beckwith–Wiedemann syndrome (BWS) disorders associated with growth retardation or overgrowth, respectively. Specific features define each of the two syndromes, but isolated asymmetry is a common cardinal feature, which is considered sufficient for a diagnosis in the BWS spectrum. Here, we report the case of a girl with right body asymmetry, which suggested BWS spectrum. Later, BWS/SRS molecular analysis identified IC1_LoM revealing the discrepant diagnosis of SRS. A clinical re-evaluation identified a relative macrocephaly and previously unidentified growth rate at lower limits of normal at birth, feeding difficulties, and asymmetry. Interestingly, and never previously described in IC1_LoM SRS patients, since the age of 16, she has developed hand-writer’s cramps, depression, and bipolar disorder. Trio-WES identified a VPS16 heterozygous variant [NM_022575.4:c.2185C>G:p.Leu729Val] inherited from her healthy mother. VPS16 is involved in the endolysosomal system, and its dysregulation is linked to autosomal dominant dystonia with incomplete penetrance and variable expressivity. IGF2 involvement in the lysosomal pathway led us to speculate that the neurological phenotype of the proband might be triggered by the concurrent IGF2 deficit and VPS16 alteration. |
| first_indexed | 2024-03-08T11:38:47Z |
| format | Article |
| id | doaj.art-c1fc1cd06de54a4d9a4c49f2e8cf8ba6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T11:38:47Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-c1fc1cd06de54a4d9a4c49f2e8cf8ba62024-01-25T11:31:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-07-011410.3389/fgene.2023.11988211198821Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrumAlessandro Vimercati0Pierpaola Tannorella1Eleonora Orlandini2Luciano Calzari3Mirella Moro4Sara Guzzetti5Angelo Selicorni6Milena Crippa7Lidia Larizza8Maria Teresa Bonati9Silvia Russo10Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalyResearch Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalySpecialty School of Pediatrics, Alma Mater University of Bologna, Bologna, ItalyBioinformatics and Statistical Genomics Unit, IRCCS Istituto Auxologico Italiano, Milano, ItalyDepartment of Endocrine and Metabolic Diseases and Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milano, ItalyResearch Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalyUOC Pediatria, ASST Lariana, Como, ItalyResearch Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalyResearch Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalyUnit of Medical Genetics, Institute for Maternal and Child Health Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofalo, Trieste, ItalyResearch Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milano, ItalyThe amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) or Gain-of-Methyaltion (GoM) causes Silver–Russell syndrome (SRS) or Beckwith–Wiedemann syndrome (BWS) disorders associated with growth retardation or overgrowth, respectively. Specific features define each of the two syndromes, but isolated asymmetry is a common cardinal feature, which is considered sufficient for a diagnosis in the BWS spectrum. Here, we report the case of a girl with right body asymmetry, which suggested BWS spectrum. Later, BWS/SRS molecular analysis identified IC1_LoM revealing the discrepant diagnosis of SRS. A clinical re-evaluation identified a relative macrocephaly and previously unidentified growth rate at lower limits of normal at birth, feeding difficulties, and asymmetry. Interestingly, and never previously described in IC1_LoM SRS patients, since the age of 16, she has developed hand-writer’s cramps, depression, and bipolar disorder. Trio-WES identified a VPS16 heterozygous variant [NM_022575.4:c.2185C>G:p.Leu729Val] inherited from her healthy mother. VPS16 is involved in the endolysosomal system, and its dysregulation is linked to autosomal dominant dystonia with incomplete penetrance and variable expressivity. IGF2 involvement in the lysosomal pathway led us to speculate that the neurological phenotype of the proband might be triggered by the concurrent IGF2 deficit and VPS16 alteration.https://www.frontiersin.org/articles/10.3389/fgene.2023.1198821/fullSilver-Russell syndromeunexpected molecular resultsbody asymmetryIGF2hand dystoniaVPS16 |
| spellingShingle | Alessandro Vimercati Pierpaola Tannorella Eleonora Orlandini Luciano Calzari Mirella Moro Sara Guzzetti Angelo Selicorni Milena Crippa Lidia Larizza Maria Teresa Bonati Silvia Russo Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum Frontiers in Genetics Silver-Russell syndrome unexpected molecular results body asymmetry IGF2 hand dystonia VPS16 |
| title | Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum |
| title_full | Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum |
| title_fullStr | Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum |
| title_full_unstemmed | Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum |
| title_short | Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum |
| title_sort | case report atypical silver russell syndrome patient with hand dystonia the valuable support of the consensus statement to the wide syndromic spectrum |
| topic | Silver-Russell syndrome unexpected molecular results body asymmetry IGF2 hand dystonia VPS16 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1198821/full |
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