Smith-Lemli-Opitz syndrome (SLOS)
General description
Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder characterized by multiple congenital malformations, intellectual disability, and distinctive biochemical abnormalities. Smith-Lemli-Opitz syndrome results from mutations in the DHCR7 gene, which encodes the enzyme 7-dehydrocholesterol reductase (DHCR7). This enzyme catalyzes the final step in cholesterol biosynthesis, converting 7-dehydrocholesterol (7-DHC) to cholesterol. The deficiency of this enzyme leads to two primary biochemical abnormalities: elevated levels of 7-DHC and frequently reduced levels of cholesterol.
Smith-Lemli-Opitz syndrome (SLOS) is marked by distinctive facial features, multiple birth defects, and abnormalities in neurodevelopment. Common craniofacial characteristics include a small head, narrowed temples, drooping eyelids, a broad and short nose with upward-facing nostrils, a small chin, and a small lower jaw. Eye issues such as cataracts, misalignment, and involuntary movement are also observed.
Limb anomalies are frequent and play an important role in diagnosis. These often include fused toes, extra fingers or toes, shortened upper limbs, and thumbs that are short and placed close to the wrist. In males, genital anomalies are commonly seen, such as small genitalia, abnormal urethral openings, and ambiguous genital structures. Additional clinical features include cleft palate, heart defects, and digestive issues like feeding problems, acid reflux, and intestinal abnormalities.
Neurodevelopmental delays are seen in all cases, though the degree varies. Individuals typically show slow growth and intellectual disability. Behavioral issues are also widespread, often involving signs consistent with autism, hyperactivity, self-harm, and sleep problems. Autism spectrum traits are especially prevalent and well-documented in those with SLOS.
References
- Lee, Ryan WY, et al. "Brain magnetic resonance imaging findings in Smith–Lemli–Opitz syndrome." American journal of medical genetics Part A 161.10 (2013): 2407-2419.
Abnormalities of the septum pellucidum
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VentricleSeptum pellucidum
Abnormalities of the septum pellucidum represent the most frequent neuroimaging finding in SLOS. These abnormalities include cavum of septum pellucidum, cavum Vergae, or cavum of velum interpositum.
Corpus callosum abnormalities
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Corpus callosum
The corpus callosum is affected in SLOS patients. Abnormalities range from complete agenesis to partial dysgenesis, hypoplasia of the rostrum or splenium, and variations in thickness.
Frontal lobe hypoplasia
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CerebrumFrontal lobe
Several abnormalities affecting the cerebral hemispheres have been documented. Hypoplastic frontal lobes are commonly observed.
Ventriculomegaly
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VentricleLateral ventriclePosterior horn
Ventriculomegaly is frequently observed in SLOS patients. This may present as enlarged lateral ventricles or, more specifically, as colpocephaly (disproportionate enlargement of the occipital horns of the lateral ventricles).
Cerebellar abnormalities
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CerebellumVermis
Cerebellar abnormalities are present in a significant proportion of patients and include cerebellar hypoplasia, sometimes with severe hypoplasia or aplasia of the vermis.