Malformation syndromes caused by disorders of cholesterol synthesis
Open accessAbstract
Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome.
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In humans, inborn errors of cholesterol synthesis induce different malformation syndromes, many of which present clinically with underdeveloped limbs, mirroring features of ulnar mammary syndrome caused by germline TBX3 mutations.
“In humans, inborn errors of cholesterol synthesis induce different malformation syndromes (35), many of which present clinically with underdeveloped limbs, mirroring features of ulnar mammary syndrome caused by germline TBX3 mutations.”
From Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion (2025) · cites this paper as [35]
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- Authors
- Porter, F. D., & Herman, G. E.
- Affiliations
- National Institutes of Health (US)
- Abigail Wexner Research Institute (US)
- ORCID
- Porter, Forbes D.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 52
- Issue
- 1
- Pages
- 6-34
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2999931
- OpenAlex
- W2123699239
- Cited by
- 473
- References
- 20
- Citations by year
- 2026: 25 · 2025: 22 · 2024: 31 · 2023: 19 · 2022: 28 · 2021: 40 · 2020: 43 · 2019: 35 · 2018: 23 · 2017: 21 · 2016: 41 · 2015: 27 · 2014: 32 · 2013: 28 · 2012: 33
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD038572, HD38572)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- cholesterol homeostasis, malformation syndromes, Smith-Lemli-Opitz syndrome, Antley-Bixler syndrome, sterol biosynthesis, congenital malformations
- MeSH terms
- Congenital Abnormalities, Abnormalities, Multiple, Animals, Cholesterol, Chondrodysplasia Punctata, Humans, Lipid Metabolism, Inborn Errors, Syndrome, Smith-Lemli-Opitz Syndrome, Steroid Metabolism, Inborn Errors, Oxidoreductases Acting on CH-CH Group Donors
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