Smith-Lemli-Opitz syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small head size (microcephaly), intellectual disability or learning problems, and behavioral problems. Many affected children have the characteristic features of autism, a developmental condition that affects communication and social interaction. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly).

The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual disability and major physical abnormalities.

ORPHANET DEFINITION A rare genetic developmental disorder characterized by multiple congenital anomalies (pre- and postnatal growth retardation, microcephaly, male genital anomalies), intellectual disability, and behavioral problems.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Prevalence at birth: 1-9 / 100 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 100 000; Slovakia; Value and class. Prevalence at birth: 1-5 / 10 000; Czech Republic; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

2-3 toe syndactyly · Very frequent (99-80%)

Syndactyly with fusion of toes two and three.

Abnormal dental morphology · Very frequent (99-80%)

An abnormality of the morphology of the tooth.

Abnormal dermatoglyphics · Very frequent (99-80%)

An abnormality of dermatoglyphs (fingerprints), which are present on fingers, palms, toes, and soles.

Anteverted nares · Very frequent (99-80%)

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Elevated 7-dehydrocholesterol · Very frequent (99-80%)

The concentration of 7-dehydrocholesterol in the blood circulation is above the upper limit of normal.

Feeding difficulties in infancy · Very frequent (99-80%)

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Gastroesophageal reflux · Very frequent (99-80%)

A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Growth delay · Very frequent (99-80%)

A deficiency or slowing down of growth pre- and postnatally.

Hypotonia · Very frequent (99-80%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Increased nuchal translucency · Very frequent (99-80%)

Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy).

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Microcephaly · Very frequent (99-80%)

Head circumference below 2 standard deviations below the mean for age and gender.

Micrognathia · Very frequent (99-80%)

Developmental hypoplasia of the mandible.

Other findings in the same source

From: Orphanet

Additional reported features include Short stature (Very frequent (99-80%)); Wide nasal bridge (Very frequent (99-80%)); Abnormal cardiovascular system morphology (Frequent (79-30%)); Abnormal lung lobation (Frequent (79-30%)); Abnormal metacarpal morphology (Frequent (79-30%)); Abnormality of the larynx (Frequent (79-30%)); Ambiguous genitalia (Frequent (79-30%)); Atrial septal defect (Frequent (79-30%)); Atrioventricular canal defect (Frequent (79-30%)); Attention deficit hyperactivity disorder (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Prevalence at birth: 1-9 / 100 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 100 000; Slovakia; Value and class. Prevalence at birth: 1-5 / 10 000; Czech Republic; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Smith-Lemli-Opitz syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Smith-Lemli-Opitz syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.