Smith-Lemli-Opitz Syndrome (SLOS) in Babies
Medically reviewed by Dr. Michael Okonkwo, MD, FAAP · Board-Certified Neonatologist
Content reviewed against published NIH, NORD, NIH guidelines
Last reviewed:
If your baby has been diagnosed with or you suspect smith-lemli-opitz syndrome (slos) in babies, here is what the evidence says.
The short answer
Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disorder caused by a deficiency of the enzyme 7-dehydrocholesterol reductase (DHCR7), which is needed for the final step of cholesterol synthesis. Low cholesterol impairs development because cholesterol is essential for cell membranes, brain development, and hormone production. Characteristic features include distinctive facial features, 2-3 toe syndactyly (webbing between the second and third toes), cleft palate, ambiguous genitalia in males, and intellectual disability. Severity varies widely. Cholesterol supplementation is the primary treatment and can improve growth and behavior.
Key takeaways
- Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disorder caused by a deficiency of the enzyme 7-dehydrocholesterol reductase (DHCR7), which is needed for the final step of cholesterol synthesis. Low cholesterol impairs development because cholesterol is essential for cell membranes, brain development, and hormone production. Characteristic features include distinctive facial features, 2-3 toe syndactyly (webbing between the second and third toes), cleft palate, ambiguous genitalia in males, and intellectual disability. Severity varies widely. Cholesterol supplementation is the primary treatment and can improve growth and behavior.
- Usually normal when: Your baby has 2-3 toe syndactyly as an isolated finding with no other features of SLOS (isolated syndactyly is common and usually benign)
- Call your doctor if: Your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight
- Varies by age — see the age-by-age breakdown below
“Fever itself is not an illness — rather, it is a sign or symptom that the body is fighting an infection. Fever stimulates certain defenses, such as the white blood cells, which attack and destroy invading bacteria.”
Parents everywhere have the same worry. You are doing the right thing by looking into it.
What Parents Should Know
According to NIH, NORD guidelines, smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disorder caused by a deficiency of the enzyme 7-dehydrocholesterol reductase (DHCR7), which is needed for the final step of cholesterol synthesis. Low cholesterol impairs development because cholesterol is essential for cell membranes, brain development, and hormone production. Characteristic features include distinctive facial features, 2-3 toe syndactyly (webbing between the second and third toes), cleft palate, ambiguous genitalia in males, and intellectual disability. Severity varies widely. Cholesterol supplementation is the primary treatment and can improve growth and behavior. At 0-3 months, sLOS may be suspected at birth based on characteristic features: small head (microcephaly), ptosis (droopy eyelids), a small upturned nose with anteverted nostrils, micrognathia (small jaw), 2-3 toe syndactyly, and in severely affected males, ambiguous genitalia or hypospadias. Cleft palate occurs in about 50% of cases. Severely affected newborns may have multiple organ malformations and feeding difficulties. Diagnosis is confirmed by elevated 7-dehydrocholesterol (7-DHC) levels in blood and genetic testing of the DHCR7 gene. Cholesterol supplementation is typically started immediately upon diagnosis. It is generally considered normal when your baby has 2-3 toe syndactyly as an isolated finding with no other features of SLOS (isolated syndactyly is common and usually benign). However, you should contact your pediatrician promptly if your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight.
Normal vs. Concerning
When to Seek Immediate Care
- Your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight
- Your baby has signs of adrenal crisis including lethargy, vomiting, poor feeding, and low blood pressure
- Your baby has signs of a heart defect such as rapid breathing, poor feeding, sweating during feeds, or bluish color
- Your child has signs of intestinal obstruction such as bilious vomiting, abdominal distension, or absence of bowel movements
By Age
What to expect by age
0-3 months
SLOS may be suspected at birth based on characteristic features: small head (microcephaly), ptosis (droopy eyelids), a small upturned nose with anteverted nostrils, micrognathia (small jaw), 2-3 toe syndactyly, and in severely affected males, ambiguous genitalia or hypospadias. Cleft palate occurs in about 50% of cases. Severely affected newborns may have multiple organ malformations and feeding difficulties. Diagnosis is confirmed by elevated 7-dehydrocholesterol (7-DHC) levels in blood and genetic testing of the DHCR7 gene. Cholesterol supplementation is typically started immediately upon diagnosis.
3-12 months
Feeding difficulties are very common and may include poor suck, vomiting, and failure to thrive. Many infants have significant irritability and tactile defensiveness (sensitivity to touch). Growth is typically poor. Cholesterol supplementation (dietary cholesterol and sometimes simvastatin in older children) is the cornerstone of treatment. Cardiac defects occur in about 50% of affected children and need evaluation. Photosensitivity (sensitivity to ultraviolet light) is common and requires sun protection.
1-3 years
Developmental delays are evident across motor, speech, and cognitive domains, though the severity is highly variable. Children on the milder end of the spectrum may walk and develop some speech, while severely affected children may have profound intellectual disability. Behavioral features can include autistic-like behaviors, self-injurious behavior, and sleep disturbances. Cholesterol supplementation may help improve behavior, growth, and development in some children. Ongoing monitoring for GI issues, kidney malformations, and adrenal insufficiency is important.
3 years+
Children with milder SLOS can make meaningful developmental progress with therapies and medical management. The behavioral profile often includes anxiety, hyperactivity, and sensory processing difficulties. Photosensitivity continues and sun avoidance with protective clothing and sunscreen is important. Some children develop pyloric stenosis or Hirschsprung disease. Lifelong cholesterol supplementation is needed. Genetic counseling is recommended for families, as SLOS is autosomal recessive with a 25% recurrence risk.
What to Tell Your Pediatrician
- Describe when you first noticed smith-lemli-opitz syndrome (slos) in babies and how it has changed over time.
- Note your baby's current age and which age-specific patterns you are seeing.
- Mention if your baby has 2-3 toe syndactyly combined with other features such as a small head, distinctive facial features, or feeding difficulties.
- Mention if your baby has unexpectedly low cholesterol on blood testing.
- Let your doctor know if you have noticed any related concerns, such as changes in feeding, sleep, or movement patterns.
- Bring a list of any questions or observations you want to discuss at the appointment.
What Should You Do?
When to take action
- Your baby has 2-3 toe syndactyly as an isolated finding with no other features of SLOS (isolated syndactyly is common and usually benign)
- Testing for SLOS (7-DHC levels) was performed and came back normal
- Your child with mild SLOS is on cholesterol supplementation and is growing and developing with appropriate therapies
- Your baby has 2-3 toe syndactyly combined with other features such as a small head, distinctive facial features, or feeding difficulties
- Your baby has unexpectedly low cholesterol on blood testing
- Your child with SLOS is having severe behavioral issues, ongoing feeding difficulties, or poor growth despite treatment
- You want to discuss genetic testing, diagnosis confirmation, or recurrence risk
- Your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight
- Your baby has signs of adrenal crisis including lethargy, vomiting, poor feeding, and low blood pressure
- Your baby has signs of a heart defect such as rapid breathing, poor feeding, sweating during feeds, or bluish color
- Your child has signs of intestinal obstruction such as bilious vomiting, abdominal distension, or absence of bowel movements
What You Can Do at Home
- Keep track of when you notice smith-lemli-opitz syndrome (slos) in babies — noting the time of day, duration, and any triggers can help your pediatrician.
- Remember that your baby has 2-3 toe syndactyly as an isolated finding with no other features of SLOS (isolated syndactyly is common and usually benign) — this is generally within the range of normal.
- At 0-3 months, focus on observation rather than intervention unless your pediatrician advises otherwise.
- Follow any care instructions from your pediatrician. Keep a written log of symptoms to bring to appointments.
- While monitoring at home, seek immediate care if your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight.
Related Conditions
Signs of a Metabolic Disorder in Babies
Metabolic disorders (inborn errors of metabolism) occur when the body cannot properly process certain nutrients or chemicals. Many are detected through newborn screening. Signs can include poor feeding, vomiting, lethargy, seizures, unusual body or urine odor, failure to thrive, developmental regression, and metabolic crises triggered by illness or fasting. Early detection and treatment are crucial, as many metabolic disorders are manageable with dietary modifications and medical treatment.
My Baby Has Webbed Fingers or Toes (Syndactyly)
Syndactyly (webbed or fused fingers or toes) is one of the most common congenital hand and foot differences, occurring in about 1 in 2,000-3,000 births. It can be simple (just skin connecting the digits) or complex (bones or other tissues fused). Webbed toes often require no treatment and do not affect function. Webbed fingers, particularly those involving the thumb or ring/small fingers, are typically treated with surgery to improve hand function. The timing and approach depend on which digits are affected.
Related Resources
Frequently asked questions
Is smith-lemli-opitz syndrome (slos) in babies normal?
When should I call the doctor about smith-lemli-opitz syndrome (slos) in babies?
When is smith-lemli-opitz syndrome (slos) in babies normal?
What causes smith-lemli-opitz syndrome (slos) in babies?
What should I mention to my pediatrician about smith-lemli-opitz syndrome (slos) in babies?
Is smith-lemli-opitz syndrome (slos) in babies normal at 0-3 months?
Is smith-lemli-opitz syndrome (slos) in babies normal at 3-12 months?
Should I go to the ER for smith-lemli-opitz syndrome (slos) in babies?
Does smith-lemli-opitz syndrome (slos) in babies go away on its own?
References
- [1]National Institutes of Health. Smith-Lemli-Opitz Syndrome. Genetic and Rare Diseases Information Center (GARD). NIH
- [2]National Organization for Rare Disorders. Smith-Lemli-Opitz Syndrome. NORD Rare Disease Database. NORD
- [3]Nowaczyk MJM, Bhatt A. Smith-Lemli-Opitz Syndrome. GeneReviews, National Library of Medicine, 2023. NIH
Doctor Visit Checklist
Bring this checklist to your next pediatrician visit to discuss Smith-Lemli-Opitz Syndrome (SLOS) in Babies.
Things to mention
- Describe when you first noticed smith-lemli-opitz syndrome (slos) in babies and how it has changed over time.
- Note your baby's current age and which age-specific patterns you are seeing.
- Mention if your baby has 2-3 toe syndactyly combined with other features such as a small head, distinctive facial features, or feeding difficulties.
- Mention if your baby has unexpectedly low cholesterol on blood testing.
- Let your doctor know if you have noticed any related concerns, such as changes in feeding, sleep, or movement patterns.
- Bring a list of any questions or observations you want to discuss at the appointment.
Observations to share
- Your baby has 2-3 toe syndactyly combined with other features such as a small head, distinctive facial features, or feeding difficulties
- Your baby has unexpectedly low cholesterol on blood testing
- Your child with SLOS is having severe behavioral issues, ongoing feeding difficulties, or poor growth despite treatment
Urgent signs to report immediately
- Your newborn with suspected or confirmed SLOS has severe feeding difficulties, is dehydrated, or is losing weight
- Your baby has signs of adrenal crisis including lethargy, vomiting, poor feeding, and low blood pressure
- Your baby has signs of a heart defect such as rapid breathing, poor feeding, sweating during feeds, or bluish color
My notes
From ismybabyalright.com — free, evidence-based baby health guides
All content follows our editorial policy and is reviewed against published clinical guidelines.
2,705 evidence-based guides6 authoritative medical sources5 medical advisory board members
Related Resources
Bottom line
Most cases of smith-lemli-opitz syndrome (slos) in babies are normal. Talk to your pediatrician if your newborn with suspected or confirmed slos has severe feeding difficulties, is dehydrated, or is losing weight.
Trust your instincts. If something feels wrong, reach out to your pediatrician. Worrying about your baby means you care — that is a good thing.
Was this page helpful?
Related Medical Concerns
Signs of a Metabolic Disorder in Babies
Metabolic disorders (inborn errors of metabolism) occur when the body cannot properly process certain nutrients or chemicals. Many are detected through newborn screening. Signs can include poor feeding, vomiting, lethargy, seizures, unusual body or urine odor, failure to thrive, developmental regression, and metabolic crises triggered by illness or fasting. Early detection and treatment are crucial, as many metabolic disorders are manageable with dietary modifications and medical treatment.
My Baby Has Webbed Fingers or Toes (Syndactyly)
Syndactyly (webbed or fused fingers or toes) is one of the most common congenital hand and foot differences, occurring in about 1 in 2,000-3,000 births. It can be simple (just skin connecting the digits) or complex (bones or other tissues fused). Webbed toes often require no treatment and do not affect function. Webbed fingers, particularly those involving the thumb or ring/small fingers, are typically treated with surgery to improve hand function. The timing and approach depend on which digits are affected.
My Baby's Head Shape Looks Abnormal
Many babies develop temporary head shape irregularities that are completely normal. A cone-shaped head from vaginal delivery reshapes within days. Mild positional flattening (plagiocephaly) from sleeping on the back is very common and usually improves with repositioning and tummy time. However, head shape changes involving ridges, a persistently bulging fontanelle, or rapid head growth changes should be evaluated to rule out craniosynostosis.
Achondroplasia (Dwarfism) in Babies
Achondroplasia is the most common form of short-limbed dwarfism, affecting about 1 in 15,000 to 40,000 births. It is caused by a mutation in the FGFR3 gene and is usually apparent at birth with characteristic features including short limbs, a larger head, and a prominent forehead. Intelligence is normal. With monitoring for specific complications and supportive care, children with achondroplasia lead full, active, and independent lives.
Adenoid Hypertrophy and Breathing
Adenoids are lymphoid tissue located behind the nose that help fight infection in young children. When adenoids become enlarged (adenoid hypertrophy), they can block the nasal airway, causing chronic mouth breathing, snoring, nasal speech, and sleep-disordered breathing. Enlarged adenoids are most common between ages 2-7 and are a leading cause of obstructive sleep apnea in young children. Treatment ranges from watchful waiting and nasal steroids to surgical removal (adenoidectomy) if breathing or sleep is significantly affected.
Adrenoleukodystrophy (ALD) in Babies
X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder affecting about 1 in 17,000 newborns, caused by mutations in the ABCD1 gene on the X chromosome. It primarily affects boys and impairs the breakdown of very long-chain fatty acids (VLCFAs), which accumulate and damage the myelin sheath in the brain and the adrenal glands. The most severe form, cerebral ALD, typically affects boys between ages 4-10 with rapid neurological decline. Newborn screening now enables early detection, and hematopoietic stem cell transplant or gene therapy performed before significant brain involvement can be life-saving.