Which syndrome is characterized by hydrocephalus, a lateral proboscis with absent nasal bone, facial microsomia, and polyhydramnios?

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Holoprosencephaly (HPE) with Cyclopia

The constellation of hydrocephalus, lateral proboscis, absent nasal bone, facial microsomia, and polyhydramnios is most consistent with alobar holoprosencephaly (HPE), specifically the severe cyclopic variant. This represents the most severe form of HPE, a midline brain malformation resulting from incomplete cleavage of the prosencephalon during early embryonic development 1.

Key Diagnostic Features

The specific combination you describe represents the most severe end of the HPE spectrum:

  • Proboscis: A tubular, nose-like appendage typically positioned above a single fused orbit (cyclopia) or between closely spaced orbits (hypotelorism)
  • Absent nasal bone: Characteristic finding in severe HPE variants
  • Facial microsomia: Reflects the severe midline facial hypoplasia
  • Hydrocephalus: Results from the alobar brain malformation with failure of normal ventricular development
  • Polyhydramnios: Common prenatal finding, likely related to impaired fetal swallowing mechanisms

Chromosomal Associations

Chromosomal abnormalities are frequently identified in HPE cases, with trisomy 13 being the most common association. However, other chromosomal anomalies can present similarly. In the case series reviewed, isochromosome 18q (resulting in trisomy 18q and monosomy 18p) was documented in a fetus with alobar HPE, cyclopia, and proboscis 1.

Prenatal Diagnosis

When these features are identified on prenatal ultrasound:

  • Structural sonography typically reveals the characteristic facial anomalies in the second trimester
  • Karyotyping or chromosomal microarray should be performed on amniotic fluid to identify underlying chromosomal abnormalities
  • Genetic counseling is essential given the high recurrence risk and lethal prognosis

Prognosis

This condition is uniformly lethal. The severity of brain malformation is incompatible with life, and most affected fetuses either die in utero or shortly after birth. The combination of alobar HPE with cyclopia and proboscis represents the most severe phenotypic expression, with no reported survivors 1.

Important Distinction

This should not be confused with:

  • Hydrolethalus syndrome: While also featuring hydrocephalus and being lethal, it presents with different facial features (not cyclopia/proboscis) and includes keyhole-shaped skull base defects and lung lobulation abnormalities 2
  • MPPH syndrome: Features megalencephaly rather than holoprosencephaly, with polymicrogyria and polydactyly 3

The presence of a proboscis with absent nasal bone is pathognomonic for severe HPE and distinguishes it from other syndromes presenting with hydrocephalus and polyhydramnios.

References

2
Research

Hydrolethalus Syndrome: A Case of a Rare Congenital Disorder.

Diagnostics (Basel, Switzerland), 2025

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