Radiology
Smith-Lemli-Opitz Syndrome
Built from Obstetric Imaging
What’s inside
10 sections · 78 slides
Overview
- What this deck covers
The disorder
What goes wrong, in which gene, and what that does to the body's cholesterol
- Definition of Smith-Lemli-Opitz syndrome
- Origin of the name RSH syndrome
- One clinical continuum rather than two types
- Spectrum of severity
- Autosomal recessive inheritance
- Autosomal recessive inheritance of an enzyme defect
- The DHCR7 gene and its enzyme
- The final step of cholesterol synthesis
- From gene fault to birth defect
- Biochemical definition of the syndrome
- Correlation of genotype with severity
- What raises 7-DHC and what lowers cholesterol
How common it is
Birth incidence, carrier rates, the populations most affected, and why so few affected babies are born
- 1:20,000
- Incidence in newborns
- Carrier frequency in specific populations
- Early pregnancy loss and low birth prevalence
- Male-to-female ratio and ascertainment bias
Why cholesterol matters to a fetus
What cholesterol is used for while a baby is being built, and what fails when it runs short
- Roles of cholesterol in fetal development
- Two ways the damage is done
- Cholesterol as a precursor of androgens
- Cholesterol and hedgehog protein activation
- Cholesterol as a component of myelin
- Maternal cholesterol supply to the fetus
Finding the condition before birth
From a low estriol on serum screening to reading the DHCR7 gene itself
- Low maternal estriol as the historical clue
- Biochemical confirmation before gene testing
- Current basis of prenatal diagnosis
- Steps in confirming the diagnosis before birth
- Difficulty of prenatal diagnosis
- Why characteristic findings are missed on ultrasound
The clinical picture
What affected children actually have, from growth and brain to heart, kidneys and skin
- Range of clinical presentation
- Growth and feeding
- Development and behaviour
- Neurologic findings
- Brain malformations
- Holoprosencephaly on prenatal ultrasound
- Undivided forebrain in a fetal brain specimen
- Craniofacial features
- Eye and ear findings
- Palate and mouth findings
- Hand and foot findings
- Extra and fused toes in a newborn
- Cardiovascular findings
- Renal findings
- Respiratory findings
- Gastrointestinal findings
- Genital findings in the male fetus
- Ambiguous genitalia in a newborn
- Skin and endocrine findings
Imaging
The ultrasound findings that should raise the possibility of Smith-Lemli-Opitz syndrome
- Ultrasound findings highly suggestive of the syndrome
- Further ultrasound pointers
- Face, great vessels and heart in a fetus with Smith-Lemli-Opitz syndrome
- Fetal profile with a small jaw and forward-tipped nostrils
- Frontal view of the fetal face
- Three-vessel view with a narrow aorta
- Four-chamber view with an atrioventricular septal defect
- Reading the four-panel ultrasound
- First-trimester findings
- Other malformations reported on prenatal ultrasound
- Role of magnetic resonance imaging
- Classic signs
Differential diagnosis
What else produces this pattern, and what to exclude before testing for SLOS
- Chromosomal conditions to exclude first
- Other syndromes with a similar presentation
- Completing the differential list
Treatment
What has been tried before birth, and what is done after it
- Prenatal treatment
- Postnatal dietary cholesterol supplementation
- Other therapies used and the evidence gap
- Surgical management of structural defects
Key messages
What the referring physician needs to know, and the points to carry away
- What the referring physician needs to know
- Obtaining a sample for molecular testing
- Key points
- References
- References (continued)
- References (continued)
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- References (continued)
- References (continued)
- Obstetric Imaging: Fetal Diagnosis and Care, 2nd Edition