Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum
Abstract
:1. Introduction
2. Biological Basis of CdLS
3. Clinical Features
Medical Problem | Prevalence |
---|---|
Gastrointestinal problems | |
-Feeding problems | frequent |
-Enteral nutrition | 40% |
-Gastro esophageal reflux | 60–75% |
-Batter esophagus | 9% |
-Eosinophilic esophagitis | 16% |
-Constipation | 10–15% |
-Gassiness | 48% |
Neurology | |
-Seizures | 45% (SMC1A gene) 15% (NIPBL gene) |
-Autonomic nervous system disfunction | 81% (mild) 26% (severe) |
-Sleep problems | 12–72% |
Orthopedics | |
-Perthes disease | 4% |
-Leg length differences | 46% |
-Congenital hip dislocation | 10% |
-Scoliosis | One third of patients after 10 years |
-Kyphosis | A quarter of patients |
-Joint contractures | 18–25% |
-Bunions | 75% |
Visual problems | |
-Palpebral ptosis | 37% (unilateral) 44% (bilateral) |
-Blepharitis | 25% |
-Nystagmus | 14–17% |
-Strabismus | 16–26% |
-Visual impairment | 44–53% |
-Pigmented peripapillary ring | 83% |
Hearing problems | |
-Conductive hearing loss | 75% |
-Neurosensorial hearing loss | 25% |
-Otitis media with effusion | 80–85% |
Immunological defects | 33% (only one specific report) [44] |
Thrombocytopenia | rare |
Cancer | No increase of risk |
4. Genotype–Phenotype Correlations
5. From Biological Basis to Future Treatment Options
5.1. Lithium
5.2. L-Leucin
5.3. Antioxidant
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Cardinal Features | Score |
---|---|
Synophrys (HP:0000664) and/or thick eyebrows (HP:0000574) | 2 |
Short nose (HP:0003196), concave nasal ridge (HP:0011120) and/or upturned nasal tip (HP:0000463) | 2 |
Long (HP:0000343) and/or smooth philtrum (HP:0000319) | 2 |
Thin upper lip vermilion (HP:0000219) and/or downturned corners of mouth (HP:0002714) | 2 |
Hand oligodactyly (HP:0001180) and/or adactyly (HP:0009776) | 2 |
Congenital diaphragmatic hernia (HP:0000776) | 2 |
Suggestive Features | |
Global developmental delay (HP:0001263) and/or intellectual disability (HP:0001249) | 1 |
Prenatal growth retardation (<2 SD) (HP:0001511) | 1 |
Postnatal growth retardation (<2 SD) (HP:0008897) | 1 |
Microcephaly (prenatally and/or postnatally) (HP:0000252) | 1 |
Small hands (HP:0200055) and/or feet (HP:0001773) | 1 |
Short fifth finger (HP:0009237) | 1 |
Hirsutism (HP:0001007) | 1 |
Interpretation of the Score | |
Score ≥11 points, of which at least 3 are cardinal features | classic CdLS |
Score between 9 or 10 points, of which at least 2 are cardinal features | non-classic CdLS |
Score between 4–8 points, of which at least 1 is cardinal feature | molecular testing for CdLS indicated |
Score <4 points | insufficient to indicate molecular testing for CdLS |
Malformation | Prevalence |
---|---|
Heart malformations (no specific defect) | 25% |
Palate | 20% |
Eyes Unilateral or bilateral nasolacrimal duct obstruction | 60–80% |
Central Nervous System | 47% (in the wider cohort reported) [35] |
Limb defects | About one third |
Urinary tract | 10% |
Genitalia | |
Cryptorchidism | 80% |
Micropenis | 37% |
Hypospadias | 9% |
Bicornuate uterus | 19% |
Gastrointestinal system | |
Intestinal malrotation | 5–10% |
Pyloric stenosis | 7% |
Diaphragmatic Hernia | rare |
Gene | Overlapping Syndrome |
---|---|
ANKRD11 | KBG syndrome |
AFF4 | CHOP syndrome |
EP300 | Rubinstein-Taybi syndrome |
KMT2A | Wiedemann-Steiner syndrome |
TAF6 | Alazami-Yuan syndrome |
SETD5 | Mental retardation, autosomal dominant 23 |
ARID1B | Coffin-Siris syndrome |
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Share and Cite
Selicorni, A.; Mariani, M.; Lettieri, A.; Massa, V. Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum. Genes 2021, 12, 1075. https://doi.org/10.3390/genes12071075
Selicorni A, Mariani M, Lettieri A, Massa V. Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum. Genes. 2021; 12(7):1075. https://doi.org/10.3390/genes12071075
Chicago/Turabian StyleSelicorni, Angelo, Milena Mariani, Antonella Lettieri, and Valentina Massa. 2021. "Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum" Genes 12, no. 7: 1075. https://doi.org/10.3390/genes12071075