Spectrum of fetal limb anomalies

Area of Science:

• Medical Genetics
• Prenatal Diagnosis
• Developmental Biology

Background:

• Antenatal detection of limb anomalies is frequent, often leading to pregnancy termination due to anticipated physical handicaps.
• Establishing accurate recurrence risks is vital for genetic counseling in families with fetal malformations.

Purpose of the Study:

• To delineate the spectrum of fetal limb anomalies detected antenatally.
• To evaluate the utility of postnatal investigations, including autopsy and genetic testing, for determining recurrence risks.
• To provide evidence supporting comprehensive postnatal evaluation for limb malformations.

Main Methods:

• Retrospective observational study of 54 cases with antenatally detected limb malformations.
• Analysis of the spectrum of limb abnormalities observed.
• Discussion on the role of fetal autopsy and genetic testing (chromosomal microarray, whole exome sequencing) in risk assessment.

Main Results:

• Radial ray anomalies were the most common isolated finding (16/54).
• Other observed conditions included amniotic band syndrome, limb-body wall complex, VACTERL association, sirenomelia, limb-pelvis hypoplasia, and OEIS complex.
• Genetic abnormalities were identified, such as trisomy 18 and Fanconi anemia, highlighting the importance of genetic testing.

Conclusions:

• Fetal autopsy is paramount in the investigation of limb anomalies.
• Chromosomal microarray (CMA) is recommended as a first-tier genetic test post-autopsy.
• Whole exome sequencing (WES) may be considered as a primary investigation in specific cases (e.g., symmetrical anomalies, consanguinity) before CMA.