[Two cases of cytopenia associated with multiple malformations]

Area of Science:

• Genetics and Molecular Biology
• Pediatric Hematology/Oncology
• Clinical Genetics

Background:

• Children presenting with hemocytopenia and congenital malformations often require complex diagnostic workups.
• Distinguishing between various genetic syndromes with overlapping clinical features is crucial for accurate diagnosis and management.
• DNA repair pathway defects can manifest with a spectrum of hematological and developmental abnormalities.

Purpose of the Study:

• To present two pediatric cases with overlapping symptoms but distinct genetic diagnoses.
• To emphasize the importance of comprehensive evaluation in children with unexplained cytopenias and dysmorphic features.
• To highlight the differential diagnosis between LIG4 syndrome and Fanconi anemia in pediatric patients.

Main Methods:

• Case report detailing clinical presentation, medical history, and physical examination findings for two pediatric patients.
• Utilized genetic testing, including whole exome sequencing or targeted gene panels, to identify causative mutations.
• Performed cytogenetic analysis, such as chromosome breakage studies, to aid in diagnosis.

Main Results:

• Patient 1: A 10-year-old girl diagnosed with LIG4 syndrome due to compound heterozygous mutations in the DNA ligase IV (LIG4) gene, presenting with pancytopenia, epistaxis, recurrent infections, café-au-lait spots, and microcephaly.
• Patient 2: A 6-year-old girl diagnosed with Fanconi anemia complementation group A, presenting with persistent thrombocytopenia, short stature, hyperpigmentation, and hand malformations, confirmed by a positive chromosome breakage test.
• Both patients exhibited overlapping features of cytopenia and malformations, yet genetic and functional test results confirmed distinct underlying molecular defects.

Conclusions:

• Clinical presentation alone can be insufficient to differentiate between genetic disorders affecting DNA repair and hematopoiesis.
• Comprehensive genetic and functional testing is essential for accurate diagnosis in pediatric patients with hemocytopenia and malformations.
• Screening for a broader range of conditions, including immune system disorders, may be warranted in cases with ambiguous findings.