Encephalocraniocutaneous lipomatosis

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Encephalocraniocutaneous lipomatosis (ECCL) is a rare condition that primarily affects the brain, eyes, and skin of the head and face. Most of this condition's signs and symptoms are present from birth, and they vary widely among affected individuals.

A hallmark feature of ECCL is a noncancerous tumor under the scalp covered by a smooth, hairless patch of skin. This type of tumor, called a nevus psiloliparus, is made up of fatty tissue. Some people with ECCL also have noncancerous tumors under the skin elsewhere on the head or face. Many have small flaps of skin called skin tags on the eyelids and around the eyes. Hair loss (alopecia), thin or missing patches of skin on the scalp (dermal hypoplasia or aplasia), and changes in skin coloring (pigmentation) are also possible.

The most common eye abnormality in ECCL is a noncancerous growth called a choristoma. These growths can be present in one or both eyes and may affect vision.

About two-thirds of people with ECCL have noncancerous fatty tumors inside the brain or around the spinal cord. These tumors are called intracranial lipomas and intraspinal lipomas, respectively. Affected individuals also have an increased risk of developing a type of brain cancer called a glioma. The brain and spinal cord abnormalities associated with ECCL can cause seizures, abnormal tensing of the muscles, and intellectual disability ranging from mild to profound. However, about one-third of affected individuals have normal intelligence.

Other kinds of growths may also occur in people with ECCL, including noncancerous jaw tumors.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

ECCL can result from mutations in the FGFR1 gene, which provides instructions for making a protein called fibroblast growth factor receptor 1 (FGFR1). This receptor interacts with proteins called fibroblast growth factors (FGFs) to trigger signaling within cells. Signaling via the FGFR1 protein is involved in many critical processes, such as cell division and the regulation of cell growth and maturation. This signaling is important for the normal development and growth of several parts of the body, including the brain.

The FGFR1 gene mutations that cause ECCL arise randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and others will not. This mixture of cells with and without a genetic mutation is known as mosaicism. In cells with an altered FGFR1 gene, the resulting FGFR1 protein is overactive, triggering abnormal signaling that affects cell growth and division. Researchers are studying how these changes in signaling lead to the growth of noncancerous tumors and the other features of ECCL.

In some people with ECCL, no FGFR1 gene mutation has been identified, and the cause of the disease is unknown. Other genetic changes are under study as possible causes of this condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is described as sporadic because it occurs in people without a history of the disorder in their family. Because ECCL results from mosaic gene mutations, which occur after conception, individuals do not inherit the condition from their parents.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

ECCL is a rare disorder. Fewer than 60 cases have been reported in the medical literature.

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.

Alopecia · Very frequent (99-80%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

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.

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.

Lipodystrophy · Very frequent (99-80%)

Degenerative changes of the fat tissue.

Multiple lipomas · Very frequent (99-80%)

The presence of multiple lipomas (a type of benign tissue made of fatty tissue).

Neurodevelopmental abnormality · Very frequent (99-80%)

A deviation from normal of the neurological development of a child, which may include any or all of the aspects of the development of personal, social, gross or fine motor, and cognitive abilities.

Retinopathy · Very frequent (99-80%)

Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.

Seizure · Very frequent (99-80%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Other findings in the same source

From: Orphanet

Additional reported features include Subcutaneous nodule (Very frequent (99-80%)); Xanthomatosis (Very frequent (99-80%)); Abnormal eyelash morphology (Frequent (79-30%)); Abnormal eyelid morphology (Frequent (79-30%)); Abnormal nasolacrimal system morphology (Frequent (79-30%)); Abnormal skull morphology (Frequent (79-30%)); Abnormality of speech or vocalization (Frequent (79-30%)); Abnormality of the face (Frequent (79-30%)); Absent septum pellucidum (Frequent (79-30%)); Agenesis of corpus callosum (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Encephalocraniocutaneous lipomatosis 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 Encephalocraniocutaneous lipomatosis. 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.