Congenital hypotonia: systematic approach for prenatal detection.

Area of Science:

• Perinatology
• Medical Genetics
• Prenatal Diagnostics

Background:

• Congenital hypotonic conditions are rare, heterogeneous, and often present subtly prenatally, hindering early detection.
• Postnatal manifestations are more prominent, but prenatal identification is critical for management and counseling.

Purpose of the Study:

• To characterize prenatal sonographic findings of congenital hypotonia throughout pregnancy.
• To evaluate the diagnostic yield of various tests for congenital hypotonia.
• To propose diagnostic models to enhance prenatal detection rates.

Main Methods:

• Retrospective observational study of singleton pregnancies with congenital hypotonia (diagnosed prenatally or postnatally).
• Assessed yield of ultrasound, fetal MRI, CT, and genetic tests (CMA, WES).
• Compared prevalence of non-specific signs (polyhydramnios, breech presentation, IUGR, reduced fetal movement) with controls.

Main Results:

• Overall prenatal detection rate was 38.5%; a targeted scan increased detection to 62.5%.
• Whole-exome sequencing (WES) identified causative mutations in 87.5% of cases where performed.
• Hypotonic fetuses showed significantly higher rates of polyhydramnios, breech presentation, IUGR, and reduced fetal movement.

Conclusions:

• Congenital hypotonic conditions are rarely detected prenatally, with signs appearing in the late second trimester.
• Targeted scans and comprehensive genetic testing (especially WES) are key for diagnosis.
• Proposed diagnostic models suggest potential for significantly increased prenatal detection rates.