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Holoprosencephaly: the Maastricht experience
U Moog1, C E De Die-Smulders, C T Schrander-Stumpel
1Department of Clinical Genetics, and Maastricht University, The Netherlands. ute.moog@gen.unimass.nl
Genetic Counseling (Geneva, Switzerland)
|November 6, 2001
Summary
Holoprosencephaly (HPE) is a brain malformation affecting forebrain cleavage. This study highlights HPE's variable severity, diverse causes including genetic factors, and proposes an etiological work-up protocol.
Area of Science:
- Developmental biology
- Clinical genetics
- Medical research
Background:
- Holoprosencephaly (HPE) is a congenital disorder resulting from incomplete forebrain division.
- It affects approximately 1 in 11,000-20,000 live births, with higher rates during embryogenesis.
- HPE presents with a wide spectrum of severity, from cyclopia to subtle craniofacial anomalies.
Observation:
- Craniofacial abnormalities are common in HPE, often correlating with developmental severity.
- Etiologies are diverse, encompassing environmental influences like maternal diabetes and genetic factors.
- Around 50% of HPE cases involve cytogenetic abnormalities (e.g., trisomy 13) or monogenic syndromes.
Findings:
- At least 12 genetic loci are implicated in HPE pathogenesis.
- Known human HPE genes include SHH, ZIC2, SIX3, and TGIF.
- Case studies revealed HPE associated with 18p deletion and SHH mutation, and submicroscopic 7q deletion in milder cases.
Implications:
- Understanding HPE's genetic basis is crucial for diagnosis and counseling.
- The study emphasizes the etiological heterogeneity and spectral nature of HPE.
- A proposed protocol aims to guide the etiological investigation of HPE cases.