Sjögren-Larsson syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Sjögren-Larsson syndrome is a condition that affects the skin and eyes as well as the brain and spinal cord (central nervous system).

Infants with Sjögren-Larsson syndrome tend to be born prematurely. At birth, the skin may be thicker than normal (hyperkeratosis) and red (erythema), but it typically becomes dry and scaly (ichthyosis). Mild to severe itchiness (pruritus) is also common. The skin abnormalities generally affect the neck, torso, arms, and legs. The face is usually not affected.

Tiny crystals in the light-sensitive tissue at the back of the eye (retina) can be seen during an eye exam in most affected individuals who are older than 3 to 4 years of age. This feature is unique to people with Sjögren-Larsson syndrome and can be used to diagnose the condition. These retinal crystals are often called “glistening white dots.” People with Sjögren-Larsson syndrome may also have nearsightedness (myopia) or an increased sensitivity to light (photophobia).

People with Sjögren-Larsson syndrome may have neurological signs and symptoms. Affected individuals often have leukoencephalopathy, which is a change in a type of brain tissue called white matter. White matter consists of nerve fibers that are covered by a substance (myelin) that insulates and protects the nerves. Leukoencephalopathy is thought to contribute to many of the neurological signs and symptoms seen in people with Sjögren-Larsson syndrome.

Most people with Sjögren-Larsson syndrome have intellectual disabilities, which can vary from mild to severe. Speech difficulties (dysarthria) are common, and speech development is often delayed. Affected individuals typically have more trouble speaking than understanding language. Approximately 35 to 40 percent of people with Sjögren-Larsson syndrome have seizures.

Children with Sjögren-Larsson syndrome typically experience abnormal muscle stiffness (spasticity) in their legs and, less commonly, in their arms. The spasticity may cause a delay in the development of motor skills such as sitting, crawling, and walking. Joint deformities (contractures) are also common. Approximately 50 percent of people with Sjögren-Larsson syndrome will require wheelchair assistance.

ORPHANET DEFINITION A rare neurocutaneous disorder caused by an inborn error of lipid metabolism and characterized by congenital ichthyosis, intellectual deficit, and spasticity.

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 / 1 000 000; Sweden; Value and class. Point prevalence: 1-5 / 10 000; Taiwan, Province of China; Value and class.

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.

Dry skin · Very frequent (99-80%)

Skin characterized by the lack of natural or normal moisture.

Erythema · Very frequent (99-80%)

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Hyperkeratosis · Very frequent (99-80%)

Hyperkeratosis is a histopathological term defining a thickened stratum corneum and may be present in many different skin conditions, with many possible overlaps. Hyperkeratosis refers to the increased thickness of the stratum corneum, the outer layer of the skin. Hyperkeratosis is subclassified as orthokeratotic or parakeratotic. Orthokeratotic hyperkeratosis refers to the thickening of the keratin layer with preserved keratinocyte maturation, while parakeratotic hyperkeratosis shows retained nuclei as a sign of delayed maturation of keratinocytes.

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.

Spastic diplegia · Very frequent (99-80%)

Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.

Spasticity · Very frequent (99-80%)

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

Generalized ichthyosis · Very frequent (99-80%)

Bilateral tonic-clonic seizure · Frequent (79-30%)

A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.

CNS demyelination · Frequent (79-30%)

A loss of myelin from nerve fibers in the central nervous system.

Cerebral dysmyelination · Frequent (79-30%)

Defective structure and function of myelin sheaths of the white matter of the brain.

Delayed CNS myelination · Frequent (79-30%)

Delayed myelination in the central nervous system.

Photophobia · Frequent (79-30%)

Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.

Pigmentary retinopathy · Frequent (79-30%)

An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Pruritus · Frequent (79-30%)

Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.

Other findings in the same source

From: Orphanet

Additional reported features include Retinal crystals (Frequent (79-30%)); Seizure (Frequent (79-30%)); Yellow/white lesions of the retina (Frequent (79-30%)); Abnormal foot morphology (Occasional (29-5%)); Abnormal metabolic brain imaging by MRS (Occasional (29-5%)); Dysarthria (Occasional (29-5%)); Dystonia (Occasional (29-5%)); Hyperreflexia (Occasional (29-5%)); Hypertonia (Occasional (29-5%)); Hypohidrosis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

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 / 1 000 000; Sweden; Value and class. Point prevalence: 1-5 / 10 000; Taiwan, Province of China; Value and class.

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 Sjögren-Larsson syndrome is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

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.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Sjögren-Larsson 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.