Prenatal Rare 16q24.1 Deletion Between Genomics and Epigenetics: A Review

Area of Science:

• Genetics
• Developmental Biology
• Medical Diagnostics

Background:

• Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, often fatal congenital disorder causing severe neonatal respiratory distress and multisystem malformations.
• ACDMPV is primarily associated with deletions or mutations in the FOXF1 gene or its regulatory regions on chromosome 16q24.1, accounting for approximately 90% of cases.

Purpose of the Study:

• To review reported prenatal cases of 16q24.1 deletions involving FOXF1.
• To identify recurrent sonographic features suggestive of ACDMPV.
• To elucidate the genomic and epigenetic mechanisms underlying ACDMPV.

Main Methods:

• Systematic literature review of prenatal cases with 16q24.1 deletions, including the FOXF1 gene.
• Inclusion of a novel case with increased nuchal translucency and a de novo 16q24.1 deletion.
• Analysis of ultrasound findings and histopathological data from reported cases.

Main Results:

• Nine prenatal cases with 16q24.1 deletions involving FOXF1 or its enhancer were identified.
• Common ultrasound findings included first-trimester increased nuchal translucency/cystic hygroma and later cardiac, renal, and intestinal malformations.
• Prenatal diagnosis solely on ultrasound is challenging; confirmation often requires post-mortem examination or termination with histological analysis.

Conclusions:

• Non-coding regulatory regions and epigenetic factors like differential methylation and imprinting significantly influence FOXF1 regulation.
• Improved prenatal diagnosis accuracy for ACDMPV requires combining array CGH or next-generation sequencing with heightened awareness of suggestive ultrasound markers.
• Further research into FOXF1 epigenetic regulation is essential for accurate recurrence risk assessment and genetic counseling.