Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver–Russell Syndrome
Abstract
:1. Introduction
2. Patients and Methods
2.1. Study Population
2.2. Clinical Assessments
2.3. Molecular Studies
2.4. Data and Statistical Analysis
3. Results
4. Discussion
Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethics Approval and Consent to Participate
Consent for Publication
Abbreviations
References
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Clinical Classification | SRS Score (Maximum = 15) | Epigenetic and Genetic Defects | ||||
---|---|---|---|---|---|---|
IC1 Hypomethylation (%) | mUPD7 (%) | Microdeletion | Unknown (%) | Molecular Diagnosis Rate | ||
Clinical diagnosis with SRS (score≥ 8) (n = 100) | 10.2 ± 1.9 | 36 (36%) | 7 (7%) | 2 (2%) | 55 (55%) | 45% |
Subjects with SRS score ≤ 7 (n = 106) | 5.3 ± 1.5 | 1 (1%) | 3 (3%) | 1 (1%) | 101 (95%) | 5% |
SRS Score (Maximum = 15) | n | IC1 Hypomethylation | mUPD7 | Microdeletion | Unknown | Molecular Diagnosis | Molecular Diagnosis Rate (%) |
---|---|---|---|---|---|---|---|
≤ 7 | 106 | 1 | 3 | 1 | 101 | 5 | 5% |
8 | 21 | 2 | 3 | 1 | 15 | 6 | 29% |
9 | 24 | 5 | 0 | 0 | 19 | 5 | 21% |
10 | 17 | 2 | 3 | 1 | 11 | 6 | 35% |
11 | 17 | 11 | 0 | 0 | 6 | 11 | 65% |
12 | 8 | 5 | 0 | 0 | 3 | 5 | 63% |
13 | 3 | 2 | 0 | 0 | 1 | 2 | 67% |
14 | 8 | 7 | 1 | 0 | 0 | 8 | 100% |
15 | 2 | 2 | 0 | 0 | 0 | 2 | 100% |
All | 206 | 37 | 10 | 3 | 156 | 50 | 24% |
Clinical Features | Clinical Diagnosis (n = 100) | p Value | Clinical Diagnosis (n = 100) | Netchine et al. [8] (n = 39) | |
---|---|---|---|---|---|
With Identified Molecular Defect (n = 43) | Without Identified Molecular Defect (n = 57) | ||||
Male/Female | 25/18 | 26/31 | 0.219 | 51/49 | 19/20 |
Age at diagnosis (years) | 4.8 ± 5.0 | 5.2 ± 3.5 | 0.717 | 5.0 ± 4.2 | — |
Height z score at diagnosis | −3.1 ± 1.6 | −2.6 ± 1.2 | 0.045 | −2.8 ± 1.4 | −3.6 ± 1.5 |
Weight z score at diagnosis | −3.0 ± 1.4 | −2.7 ± 1.2 | 0.262 | −2.8 ± 1.3 | — |
Gestational age (weeks) | 37.9 ± 1.7 (n = 41) | 37.3 ± 3.0 (n = 54) | 0.288 | 37.5 ± 2.5 (n = 95) | 37.5 ± 2.8 |
Birth length z score | −4.1 ± 1.6 (n = 26) | −2.5 ± 1.4 (n = 38) | <0.001 | −2.7 ± 1.0 (n = 64) | −4.1 ± 1.5 |
Birth weight z score | −3.0 ± 0.9 (n = 40) | −2.4 ± 1.0 (n = 54) | 0.009 | −3.1 ± 1.7 (n = 94) | −3.1 ± 1.2 |
Birth OFC z score | −1.2 ± 2.6 (n = 22) | −1.8 ± 1.7 (n = 30) | 0.309 | −1.5 ± 2.1 (n = 52) | −1.5 ± 1.1 |
Paternal age at childbirth (years) | 33.7 ± 4.8 (n = 29) | 34.4 ± 5.2 (n = 40) | 0.590 | 34.1 ± 5.0 (n = 69) | — |
Maternal age at childbirth (years) | 31.3 ± 4.8 (n = 29) | 31.7 ± 5.1 (n = 40) | 0.755 | 31.6 ± 4.9 (n = 69) | — |
Parameters at birth | |||||
Weight ≤ 10th centile | 98% | 86% | 0.043 | 91% | — |
Length ≤ 10th centile | 98% | 84% | 0.026 | 90% | — |
Relative macrocephaly | 86% | 33% | <0.001 | 56% | 84.6% |
Postnatal course | |||||
No catch-up growth; height ≤ 3rd centile | 93% | 88% | 0.387 | 90% | 92.3% |
Normal head circumference; OFC ≥ 3rd centile and ≤97th centile | 88% | 60% | 0.001 | 72% | — |
Normal cognitive development | 86% | 68% | 0.041 | 76% | 76.9% |
Asymmetry | |||||
Face/body/limbs | 77% | 56% | 0.033 | 65% | 64.1% |
Facial features | |||||
Triangular shaped face | 84% | 88% | 0.573 | 86% | — |
High/bossing forehead | 84% | 79% | 0.552 | 81% | 92.3% |
Other: e.g., small chin, thin lips, downturned corners of the mouth, late closure of fontanelle | 67% | 65% | 0.794 | 66% | — |
Other features | |||||
Clinodactyly of the fifth finger | 63% | 63% | 0.970 | 63% | 64.1% |
Genital abnormalities (e.g., cryptorchidism, hypospadias) | 16% | 14% | 0.759 | 15% | — |
Other: e.g., brachymesophalangy, syndactyly toes, inguinal hernia, pigmentary changes | 33% | 40% | 0.429 | 37% | 17.9% |
Total score (maximum = 15) | 11.3 ± 2.1 | 9.4 ± 1.2 | <0.001 | 10.2 ± 1.9 | — |
Clinical Features | IC1 Hypomethylation (n = 37) | mUPD7 (n = 10) | p Value |
---|---|---|---|
Male/Female | 23/14 | 4/6 | 0.217 |
Age at diagnosis (years) | 4.4 ± 4.1 | 6.1 ± 7.4 | 0.355 |
Height z score at diagnosis | −3.0 ± 1.7 | −3.8 ± 1.2 | 0.199 |
Weight z score at diagnosis | −3.0 ± 1.5 | −3.2 ± 1.4 | 0.639 |
Gestational age (weeks) | 38.0 ± 1.7 (n = 35) | 36.6 ± 1.6 (n = 9) | 0.026 |
Birth length z score | −4.1 ± 1.8 (n = 23) | −3.7 ± 0.9 (n = 5) | 0.578 |
Birth weight z score | −3.0 ± 0.9 (n = 34) | −2.5 ± 0.9 (n = 9) | 0.150 |
Birth OFC z score | −1.3 ± 1.3 (n = 20) | −1.6 ± 1.1 (n = 4) | 0.800 |
Paternal age at childbirth (years) | 32.9 ± 4.3 (n = 25) | 37.6 ± 4.8 (n = 7) | 0.018 |
Maternal age at childbirth (years) | 30.3 ± 4.1 (n = 25) | 35.3 ± 5.1 (n = 7) | 0.011 |
Parameters at birth | |||
Weight ≤ 10th centile | 97% | 100% | 0.609 |
Length ≤ 10th centile | 100% | 90% | 0.053 |
Relative macrocephaly | 89% | 50% | 0.004 |
Postnatal course | |||
No catch-up growth; height ≤ 3rd centile | 92% | 100% | 0.363 |
Normal head circumference; OFC ≥ 3rd centile and ≤ 97th centile | 89% | 80% | 0.451 |
Normal cognitive development | 86% | 80% | 0.618 |
Asymmetry | |||
Face/body/limbs | 76% | 50% | 0.120 |
Facial features | |||
Triangular shaped face | 89% | 50% | 0.004 |
High/bossing forehead | 81% | 80% | 0.940 |
Other: e.g., small chin, thin lips, downturned corners of the mouth, late closure of fontanelle | 68% | 60% | 0.662 |
Other features | |||
Clinodactyly of the fifth finger | 68% | 20% | 0.006 |
Genital abnormalities (e.g., cryptorchidism, hypospadias) | 19% | 0% | 0.142 |
Others: e.g., brachymesophalangy, syndactyly toes, inguinal hernia, pigmentary changes | 35% | 10% | 0.128 |
Total score (maximum = 15) | 11.4 ± 2.2 | 8.7 ± 2.5 | 0.001 |
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Lin, H.-Y.; Lee, C.-L.; Fran, S.; Tu, R.-Y.; Chang, Y.-H.; Niu, D.-M.; Chang, C.-Y.; Chiu, P.-C.; Chou, Y.-Y.; Hsiao, H.-P.; et al. Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver–Russell Syndrome. J. Pers. Med. 2021, 11, 1197. https://doi.org/10.3390/jpm11111197
Lin H-Y, Lee C-L, Fran S, Tu R-Y, Chang Y-H, Niu D-M, Chang C-Y, Chiu P-C, Chou Y-Y, Hsiao H-P, et al. Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver–Russell Syndrome. Journal of Personalized Medicine. 2021; 11(11):1197. https://doi.org/10.3390/jpm11111197
Chicago/Turabian StyleLin, Hsiang-Yu, Chung-Lin Lee, Sisca Fran, Ru-Yi Tu, Ya-Hui Chang, Dau-Ming Niu, Chia-Ying Chang, Pao-Chin Chiu, Yen-Yin Chou, Hui-Pin Hsiao, and et al. 2021. "Epigenotype, Genotype, and Phenotype Analysis of Taiwanese Patients with Silver–Russell Syndrome" Journal of Personalized Medicine 11, no. 11: 1197. https://doi.org/10.3390/jpm11111197