Cornelia de Lange Syndrome: Key Clinical Signs, Growth Delay, and Differential Diagnosis with NIPBL Genetic Testing

The Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by a series of congenital anomalies and growth delay. This syndrome serves as a paradigmatic example of chromatinopathies, a group of neurodevelopmental disorders caused by mutations affecting proteins responsible for chromatin remodeling and transcriptional regulation. Clinical manifestations include intellectual disability, synophrys, and limb anomalies, among others.

Key Clinical Signs and Differential Diagnosis

The diagnosis of CdLS is based on the identification of distinctive clinical features, such as synophrys, long eyelashes, and growth delay. However, diagnostic confirmation is achieved through genetic testing, particularly by looking for mutations in the NIPBL gene, which is responsible for the majority of cases. Automated facial analysis technology has proven useful in identifying dysmorphic phenotypes associated with CdLS, showing a detection rate comparable to that of dysmorphology experts [2].

CdLS shares clinical features with other congenital syndromes, complicating the differential diagnosis. For instance, Wiedemann-Steiner syndrome and Rubinstein-Taybi syndrome present phenotypes that overlap with CdLS due to alterations in genes regulating chromatin [4]. Next-generation sequencing is a valuable tool for differentiating between these syndromes [5].

Conclusions

The Cornelia de Lange syndrome is a complex disorder that requires thorough clinical and genetic evaluation for accurate diagnosis. Identifying key clinical signs and utilizing genetic testing are essential for differentiating it from other congenital syndromes with overlapping features. Understanding chromatinopathies and their impact on neurodevelopment is crucial for improving the management and treatment of patients with CdLS [1].

Referencias

• [1] Cornelia de Lange Syndrome as Paradigm of Chromatinopathies
• [2] Recognition of the Cornelia de Lange syndrome phenotype with facial dysmorphology novel analysis
• [4] Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report
• [5] Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes

Created 13/1/2025