CASE STUDY: CONGENITAL ANOMALIES, RARE DISEASES AND INHERITED DISORDERS 🎗

“Genomic medicine has the potential to transform the diagnosis and treatment of rare diseases.” - Dr. Eric D. Green

🧬 Congenital anomalies, rare diseases and inherited disorders are central to human genetics because they reveal how genomic, chromosomal and environmental factors influence development and lifelong health. Congenital anomalies may arise from genetic variants, chromosomal abnormalities, infections, nutritional factors or gene-environment interactions. Although individual rare diseases are uncommon, collectively they affect millions worldwide.

🔹 Down syndrome is most commonly caused by trisomy 21 and hints the importance of cytogenetics, prenatal screening, diagnostic testing and genetic counselling. Non-invasive prenatal testing (NIPT) has substantially improved screening accuracy, although positive screening results require diagnostic confirmation. Importantly, genomic information should support (not define) expectations about an individual's abilities, health or quality of life.

🔹 Cystic fibrosis (CF) results from pathogenic variants in the CFTR gene. Carrier screening, newborn screening and molecular diagnosis enable earlier intervention. The CFTR-modulator era demonstrates how genotype-informed medicine can move beyond diagnosis toward targeted treatment, while theratyping and emerging gene-based approaches may extend options for individuals with difficult-to-treat variants.

  🔹 Spinal muscular atrophy (SMA) demonstrates the clinical value of early genomic diagnosis. SMN1-related SMA can cause progressive motor-neuron loss, but newborn screening can identify affected infants before symptoms appear. Evidence increasingly supports presymptomatic treatment, illustrating how genomic diagnosis can directly change disease trajectories.

➡ Phenylketonuria (PKU) remains a classic example of successful population screening. Early identification through newborn screening allows dietary and pharmacological interventions before irreversible neurological injury occurs. Current research is expanding newborn screening from biochemical testing toward increasingly integrated genomic approaches.

⚠ In an Oystershell, congenital anomalies, rare diseases and inherited disorders cases demonstrate a continuum from prenatal testing, carrier screening, newborn screening, molecular diagnosis, precision therapy, to lifelong care. Recent evidence shows increasing diagnostic value from exome or genome sequencing, including prenatal sequencing for selected fetal anomalies and genome sequencing for previously undiagnosed rare diseases.

Abubakar Abubakar ✍️

• Pandey R, et al. Genet Med. 2025;27(6):101398.

• Tümmler B, et al. Mol Cell Pediatr. 2025;12:6.

#HumanGenetics #GenomicMedicine #RareDiseases #CongenitalAnomalies #InheritedDisorders #PrecisionMedicine #PrenatalTesting #NewbornScreening #GeneTherapy #CRISPR #NGS #PGT #IVF #ART ⚕