Beckwith-Wiedemann syndrome due to CDKN1C mutation
General Information (adopted from Orphanet):
| Synonyms, Signs: |
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| Number of Symptoms | 47 |
| OrphanetNr: | 231120 |
| OMIM Id: |
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| ICD-10: |
Q87.3 |
| UMLs: |
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| MeSH: |
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| MedDRA: |
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| Snomed: |
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Prevalence, inheritance and age of onset:
| Prevalence: | No data available. |
| Inheritance: |
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| Age of onset: |
Antenatal Neonatal 8841187 [IBIS] |
Disease classification (adopted from Orphanet):
| Parent Diseases: |
Beckwith-Wiedemann syndrome
-Rare cardiac disease -Rare developmental defect during embryogenesis -Rare genetic disease -Rare maxillo-facial surgical disease -Rare oncologic disease -Rare otorhinolaryngologic disease -Rare renal disease |
Comment:
| CDKN1C is imprinted and only the maternal allele is expressed in both mice and humans. Two patients were heterozygous for different mutations in this gene - a missense mutation in the Cdk inhibitory domain resulting in loss of most of the protein, and a frameshift resulting in disruption of the QT domain. The missense mutation was transmitted from the patient's carrier mother, indicating that the expressed maternal allele was mutant and that the repressed paternal allele was normal (PMID:8841187). A small number of individuals with Beckwith-Wiedemann syndrome (5-10%) have mutations in CDKN1C, a cyclin-dependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation (PMID:20503313). Point mutations in CDKN1C, a cyclin-dependent kinase inhibitor acting as negative regulator of cell proliferation, have been found in 5–7% of sporadic BWS cases and in approximately 40% of cases with a positive family history (PMID:21248736). |
Symptom Information:
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(HPO:0002558) | Supernumerary nipple | 20503313 | IBIS | 40 / 7739 | ||
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(HPO:0004464) | Postauricular pit | 20503313 | IBIS | 3 / 7739 | ||
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(HPO:0000486) | Strabismus | 20503313 | IBIS | 576 / 7739 | ||
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(HPO:0001520) | Large for gestational age | Frequent [IBIS] | 8841187; 11414765 | IBIS | 34 / 7739 | |
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(HPO:0001943) | Hypoglycemia | Frequent [IBIS] | 20503313; 10424811; 9311734; 11414765 | IBIS | 131 / 7739 | |
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(HPO:0001998) | Neonatal hypoglycemia | 8841187 | IBIS | 22 / 7739 | ||
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(HPO:0001629) | Ventricular septal defect | 20503313 | IBIS | 316 / 7739 | ||
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(HPO:0001643) | Patent ductus arteriosus | 20503313 | IBIS | 228 / 7739 | ||
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(HPO:0000158) | Macroglossia | Frequent [IBIS] | 8841187; 20503313; 9311734; 11414765; 9311733 | IBIS | 119 / 7739 | |
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(HPO:0003006) | Neuroblastoma | 9311734 | IBIS | 16 / 7739 | ||
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(HPO:0011398) | Central hypotonia | 20503313 | IBIS | 12 / 7739 | ||
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(HPO:0010442) | Polydactyly | 20503313 | IBIS | 69 / 7739 | ||
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(HPO:0001528) | Hemihypertrophy | Rare [IBIS] | 25898929 | IBIS | 13 / 7739 | |
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(HPO:0002240) | Hepatomegaly | 20503313 | IBIS | 467 / 7739 | ||
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(HPO:0001744) | Splenomegaly | 20503313 | IBIS | 337 / 7739 | ||
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(HPO:0003271) | Visceromegaly | Occasional [IBIS] | 10424811; 25898929 | IBIS | 8 / 7739 | |
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(HPO:0010866) | Abdominal wall defect | Frequent [IBIS] | 20503313; 10424811; 8841187 | IBIS | 5 / 7739 | |
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(HPO:0001540) | Diastasis recti | Rare [IBIS] | 25898929 | IBIS | 23 / 7739 | |
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(HPO:0001537) | Umbilical hernia | Occasional [IBIS] | 20503313; 10424811 | IBIS | 206 / 7739 | |
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(HPO:0000023) | Inguinal hernia | 20503313; 11414765 | IBIS | 181 / 7739 | ||
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(HPO:0001539) | Omphalocele | Frequent [IBIS] | 23719190; 8841187; 20503313; 10424811; 11106355; 9311734; 9311734; 11414765; 9311733; 25898929 | IBIS | 102 / 7739 | |
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(HPO:0004392) | Prune belly | 10424811 | IBIS | 4 / 7739 | ||
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(HPO:0000047) | Hypospadias | 20503313 | IBIS | 250 / 7739 | ||
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(HPO:0000028) | Cryptorchidism | 20503313; 9311734 | IBIS | 347 / 7739 | ||
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(HPO:0000271) | Abnormality of the face | Frequent [IBIS] | 11414765 | IBIS | 108 / 7739 | |
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(HPO:0000280) | Coarse facial features | 11414765 | IBIS | 189 / 7739 | ||
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(HPO:0000175) | Cleft palate | 23719190; 20503313; 25898929 | IBIS | 349 / 7739 | ||
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(HPO:0000356) | Abnormality of the outer ear | Frequent [IBIS] | 11414765; 9311733; 25898929 | IBIS | 85 / 7739 | |
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(HPO:0000363) | Abnormality of earlobe | 10424811; 9311734 | IBIS | 4 / 7739 | ||
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(HPO:0009908) | Anterior creases of earlobe | 8841187; 20503313; 11414765 | IBIS | 10 / 7739 | ||
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(HPO:0002104) | Apnea | 20503313 | IBIS | 106 / 7739 | ||
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(HPO:0001052) | Nevus flammeus | Occasional [IBIS] | 8841187; 20503313; 10424811; 9311734; 25898929 | IBIS | 88 / 7739 | |
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(HPO:0003765) | Psoriasis | 20503313 | IBIS | 17 / 7739 | ||
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(HPO:0010609) | Skin tags | 11414765 | IBIS | 12 / 7739 | ||
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(HPO:0000077) | Abnormality of the kidney | Occasional [IBIS] | 20503313; 25898929 | IBIS | 73 / 7739 | |
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(HPO:0000105) | Enlarged kidneys | Frequent [IBIS] | 20503313 | IBIS | 30 / 7739 | |
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(HPO:0000107) | Renal cyst | 20503313 | IBIS | 126 / 7739 | ||
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(HPO:0002597) | Abnormality of the vasculature | 11414765 | IBIS | 5 / 7739 | ||
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(HPO:0002898) | Embryonal neoplasm | Rare [IBIS] | 25898929 | IBIS | 6 / 7739 | |
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(HPO:0001548) | Overgrowth | Frequent [IBIS] | 8841187; 20503313 | IBIS | 27 / 7739 | |
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(HPO:0001622) | Premature birth | 25898929 | IBIS | 100 / 7739 | ||
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(HPO:0030025) | Auricular pit | 20503313; 9311734 | IBIS | 3 / 7739 | ||
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(HPO:0003396) | Syringomyelia | 11414765 | IBIS | 16 / 7739 | ||
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(HPO:0002144) | Tethered cord | 11414765 | IBIS | 8 / 7739 | ||
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(MedDRA:10061998) | Hepatic lesion | 11414765 | IBIS | 1 / 7739 | ||
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(OMIM) | Craniofacial anomalies | 9311734 | IBIS | 2 / 7739 | ||
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(OMIM) | Cutaneous vascular malformations | 20503313 | IBIS | 2 / 7739 |
Associated genes:
| CDKN1C; |
ClinVar (via SNiPA)
| Gene symbol | Variation | Clinical significance | Reference |
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