CDKN1C -Related Beckwith-Wiedemann Syndrome: First Patient from India

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.