Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management
Abstract
:1. Introduction
2. Overview of Prosencephalic Development
3. Radiologic Classification of HPE
4. Clinical Features
4.1. Craniofacial Defects and Developmental Outcomes
4.1.1. Alobar HPE
4.1.2. Semilobar HPE
4.1.3. Lobar HPE and MIH Variant
4.2. Survival
4.3. Other Common Clinical Features
5. Etiology
5.1. Genetic Causes
5.1.1. Chromosomal Anomalies
5.1.2. Monogenic Causes
- Non-syndromic monogenic causes
- Syndromic monogenic causes
- Smith–Lemli–Opitz syndrome (SLOS)
- Steinfield syndrome
- FGFR1-related syndromes
- Stromme syndrome
5.2. Non-Genetic Factors
6. Investigations and Management
6.1. Brain Imaging
6.2. Genetic Testing
6.3. Considerations Related to Prenatal Diagnosis and Genetic Counseling
6.4. Management
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type | Main Features | References |
---|---|---|
Alobar | Absent separation of the cerebral hemispheres; Single “monoventricle”; Agenesis of the corpus callosum, absent third ventricle; Fusion of thalami and basal ganglia; Dorsal cyst is frequent; Significant midline facial defects. | [6,14,16,19,20] |
Semilobar | Anterior lobes fail to separate; Interhemispheric fissure detected only posteriorly; Small, partially-formed third ventricle is often noted; Dorsal cyst may also be present; Midline craniofacial defects may be present or only subtle facial abnormalities. | [6,16] |
Lobar | Only the most rostral-inferior parts of the frontal lobes are fused; Septum pellucidum is usually absent; Posterior half of the corpus callosum is formed; Varying degrees of basal ganglia and thalamic fusion; Midline craniofacial defects often absent or mild. | [6,16,21] |
Middle interhemispheric variant (syntelencephaly) | Failure of separation of the posterior frontal and parietal lobes; Variable lack of cleavage of the basal ganglia and thalami; Absence of the body but presence of the genu and splenium of the corpus callosum. | [6,16,17,22] |
Septopreoptic (minimal form) | Midline fusion restricted to the septal region or preoptic region of the telencephalon. | [16] |
Microform | Only HPE-related subtle craniofacial anomalies; No structural brain defects on imaging. | [16] |
Genetic Causes | |||
---|---|---|---|
Syndromic | Non-Syndromic | ||
Chromosomal | Monogenic | ||
Aneuploidies | Structural Abnormalities | ||
Trisomy 13 (Patau syndrome) Trisomy 18 (Edwards syndrome) | del or dup(13q) del(18p) del(7)(q36) dup(3)(p24-pter) del(2)(p21) del(21)(q22.3) | CDON-Steinfeld syndrome | SHH (AD, MIM#142945) |
(AD, MIM#184705) | ZIC2 (AD, MIM#609637) | ||
FGFR1-Kallmann syndrome 2 | SIX3 (AD, MIM#157170) | ||
(AD, MIM# #147950) | TGIF1 (AD, MIM#142946) | ||
FGFR1-Hartsfield syndrome | GLI2 (AD, MIM#610829) | ||
(AD, MIM#615465) | FGF8 (AD, MIM#612702) | ||
CENPF-Stromme syndrome | FGFR1 (AD, MIM#147950) | ||
(AR, MIM#243605) | DISP1 (AD, MIM#612530) | ||
DHCR7-Smith-Lemli-Optiz syndrome | DLL1 (AD, MIM#618709) | ||
(AR, MIM#270400) | CDON (AR, MIM#614226) |
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Malta, M.; AlMutiri, R.; Martin, C.S.; Srour, M. Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management. Children 2023, 10, 647. https://doi.org/10.3390/children10040647
Malta M, AlMutiri R, Martin CS, Srour M. Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management. Children. 2023; 10(4):647. https://doi.org/10.3390/children10040647
Chicago/Turabian StyleMalta, Maísa, Rowim AlMutiri, Christine Saint Martin, and Myriam Srour. 2023. "Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management" Children 10, no. 4: 647. https://doi.org/10.3390/children10040647