Fetal cystic biliary lesion with absent gallbladder (Cystic biliary atresia)

Maternal hypertrichosis and synophrys

Suspicion of syndromic background

Clinical Clue

Mother has hypertrichosis; synophrys

Fetus has cystic biliary anomaly with absent gallbladder

In many families:

• The mother may have mild or mosaic CdLS
• The fetus may have more severe disease

Biliary Anomalies Can Occur in CdLS

Hepatobiliary abnormalities are documented in Cornelia de Lange syndrome.

Reported hepatobiliary features include:

• Absent or small gallbladder
• Biliary dysgenesis
• Cholestasis
• Biliary atresia–like presentations
• Feeding and GI dysmotility

CdLS genes affect: Cohesin complex → organ morphogenesis → ductal plate development

Cystic biliary atresia + maternal CdLS traits → raises suspicion for familial CdLS.

Maternal Phenotype: Very Important

• Hypertrichosis
• Synophrys

Other subtle maternal signs worth checking:

• Short stature
• Small hands
• Mild learning difficulty
• High-arched palate
• Thin upper lip
• Long philtrum

Mosaic or mildly affected adults

Genetic Background

Most CdLS cases are: De novo

Familial transmission does occur, especially with:

• NIPBL gene mutations
• SMC1A gene variants (X-linked)
• HDAC8 gene variants

Maternal mosaicism is well documented.

This explains: Mild maternal features & Severe fetal disease

Maternal Mosaic CdLS

Leading to: Fetal CdLS with biliary anomaly

This fits: Subtle maternal phenotype → syndromic fetus

Autosomal dominant developmental syndromes

With: Variable expressivity

CdLS is a classic example.

Conclusion

Fetal cystic biliary atresia

With: Possible familial or mosaic CdLS

Especially given maternal facial phenotype.