CDKN1C -Related Beckwith-Wiedemann Syndrome: First Patient from India
Veronica Arora1, Aashita Takkar1, Sudhisha Dubey1
1Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.
Insights
Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth disorder. A rare genetic variant in the CDKN1C gene was identified as the cause of BWS in a young boy, impacting cell cycle regulation and growth inhibition.
Area of Science:
- Genetics
- Pediatrics
- Molecular Biology
Background:
- Beckwith-Wiedemann syndrome (BWS) is a recognized pediatric overgrowth disorder.
- Pathogenic variants in the CDKN1C gene are implicated in approximately 5% of BWS cases.
- The CDKN1C gene encodes the p57 (KIP2) protein, a crucial inhibitor of cyclin-dependent kinases (CDKs) regulating cell cycle progression.
Purpose of the Study:
- To describe a case of BWS caused by a specific maternally inherited CDKN1C variant.
- To detail the natural history and evolving facial features in a patient with BWS.
- To provide insights into genotype-phenotype correlations and differential diagnoses for BWS.
Main Methods:
- Case report of a 2.5-year-old boy diagnosed with BWS.
- Genetic analysis to identify variants in the CDKN1C gene.
- Clinical observation of the patient's developmental trajectory and physical characteristics.
Main Results:
- A maternally inherited variant (c.182G>T, p.Trp61Cys) in the CDKN1C gene was identified as the cause of BWS.
- The variant leads to a loss of inhibitory function of CDK, impairing growth inhibition and resulting in the BWS phenotype.
- The study documents the clinical presentation and natural progression of the disorder in the affected child.
Conclusions:
- This case highlights a rare genetic mechanism underlying a common overgrowth syndrome.
- Understanding the genotype-phenotype correlation is essential for accurate diagnosis and management of BWS.
- Salient diagnostic and management features of BWS associated with CDKN1C variants are emphasized.
Abstract:
Beckwith-Wiedemann syndrome (BWS; MIM# 130650) is a well-characterized pediatric overgrowth disorder. In approximately 5% of the cases, it is caused by pathogenic variants in the CDKN1C (cyclin-dependent kinase inhibitor 1C). CDKN1C gene encodes for a protein p57 (KIP2) that acts as an inhibitor of cyclin-dependent kinases (CDK) that are expressed in the G and S-phase of the cell cycle, thus regulating cellular proliferation. Variants in CDKN1C gene lead to loss of inhibitory function of CDK and thus impair the inhibition of growth, resulting in BWS phenotype. We describe here a 2.5-year-old boy with a maternally inherited variant c.182G > T, p.Trp61Cys in the CDKN1C gene causing BWS. The natural history of the disorder is described along with the gradual change in the facial features. An insight into the genotype-phenotype correlation and disorders to be considered in the differential diagnosis is provided. We describe a common overgrowth syndrome with its rare genetic mechanism and highlight the salient features that help in making a diagnosis and managing patients.
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