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Encephalocraniocutaneous Lipomatosis

Encephalocraniocutaneous Lipomatosis (ECCL; Haberland syndrome) — Disease Characteristics Research Report

2026-05-08
Falcon MONDO:0013074 Model: Edison Scientific Literature 41 citations

Encephalocraniocutaneous Lipomatosis (ECCL; Haberland syndrome) — Disease Characteristics Research Report

Target disease

Encephalocraniocutaneous lipomatosis (ECCL) is a rare, congenital neurocutaneous syndrome characterized by a triad of cutaneous, ocular, and central nervous system (CNS) malformations that are often patchy/asymmetric, consistent with postzygotic mosaicism. (bennett2016mosaicactivatingmutations pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 1-2)

Scope note (evidence type): The ECCL knowledge base evidence base is primarily aggregated from published case reports/series and reviews (e.g., Moog’s 54-case synthesis) rather than from population-scale cohorts or EHR-derived datasets. (moog2009encephalocraniocutaneouslipomatosis pages 5-6, moog2009encephalocraniocutaneouslipomatosis pages 1-2)

1. Disease information

1.1 Concise overview / definition

ECCL is a sporadic congenital condition with ocular, cutaneous, and CNS involvement; hallmark lesions include nevus psiloliparus (alopecic fatty scalp nevus), ocular choristomas (epibulbar dermoids/lipodermoids), and intracranial/intraspinal lipomas and related brain malformations. (bennett2016mosaicactivatingmutations pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 5-6)

1.2 Key identifiers and synonyms

Not found in retrieved full texts (flag for external verification): MONDO ID, MeSH heading, ICD-10/ICD-11 codes. (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4)

2. Etiology

2.1 Disease causal factors (genetic/mechanistic)

Current understanding: ECCL is best understood as a mosaic developmental RAS/MAPK-pathway disorder (a mosaic RASopathy spectrum disorder). Multiple genetic mechanisms can converge on RAS-MAPK signaling upregulation:

1) Postzygotic mosaic activating FGFR1 variants (primary established mechanism) - Bennett et al. identified recurrent FGFR1 kinase-domain mosaic variants in affected tissues (not reliably in blood), including FGFR1 c.1638C>A (p.Asn546Lys; N546K) and c.1966A>G (p.Lys656Glu; K656E). (bennett2016mosaicactivatingmutations pages 1-2) - Functional studies in ECCL fibroblast cell lines showed increased phosphorylated FGFR/FRS2 and constitutive downstream signaling consistent with RAS-MAPK pathway activation. (bennett2016mosaicactivatingmutations pages 1-2)

2) Postzygotic KRAS variants (codon 146 hotspot) - ECCL is described as a sporadic RASopathy in which mosaic FGFR1 hotspot variants are common; a 2024 neuroradiology case report of ECCL with diffuse leptomeningeal glioneural tumor (DL-GNT) reported a KRAS codon 146 mutation in the patient described. (ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3)

3) Alternative convergent pathway mechanism via NF1 (recent development) - A 2024 Journal of Medical Genetics report described an ECCL phenotype explained by early embryonic mosaic biallelic NF1 inactivation (germline NF1 nonsense plus somatic second hit on the other allele) localized to affected tissues, arguing that distinct mosaic mechanisms can produce an ECCL phenotype by converging on the RAS-MAPK pathway. (smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 1-6)

2.2 Risk factors and protective factors

  • Risk factors: For most patients, ECCL arises sporadically via postzygotic events; familial risk is not supported by available evidence (no recurrence in siblings/offspring reported in Moog’s synthesis). (moog2009encephalocraniocutaneouslipomatosis pages 7-8)
  • Protective factors / gene–environment interactions: Not reported in retrieved evidence; ECCL is not described as environmentally triggered in available sources.

3. Phenotypes (with frequencies, when available)

Moog (2009) synthesized 54 ECCL cases and provides the most commonly cited quantitative phenotype frequencies in retrieved evidence. (moog2009encephalocraniocutaneouslipomatosis pages 5-6)

3.1 Core phenotypes and frequencies (selected)

Additional frequency estimates (Bennett 2016 excerpt): nevus psiloliparus and ocular choristomas each ~80%; intracranial/intraspinal lipomas ~61%. (bennett2016mosaicactivatingmutations pages 1-2)

3.2 Phenotype ontology suggestions (examples)

Selected HPO mappings are summarized in the phenotype table artifact. (moog2009encephalocraniocutaneouslipomatosis pages 5-6, moog2009encephalocraniocutaneouslipomatosis pages 1-2)

4. Genetic / molecular information

4.1 Causal genes and variant classes

4.2 Somatic vs germline

ECCL is primarily described as postzygotic constitutional mosaicism, with variants often absent from peripheral blood; sensitive detection from affected tissue is frequently required. (bennett2016mosaicactivatingmutations pages 1-2, kordacka2019sensitivedetectionof pages 1-2)

4.3 Functional consequences / pathway

4.4 Population allele frequency

Population allele frequency information (gnomAD/ExAC/TOPMed) was not available in retrieved full-text evidence; variants are typically mosaic and thus not expected at appreciable germline frequencies.

5. Environmental information

No specific environmental/lifestyle or infectious contributors are described in retrieved evidence; ECCL is treated as a congenital developmental mosaic condition. (bennett2016mosaicactivatingmutations pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 7-8)

6. Mechanism / pathophysiology

6.1 Causal chain (current model)

A plausible causal chain is: 1) Early embryonic postzygotic mutation (most often FGFR1 activation; sometimes KRAS activation; rarely NF1 biallelic inactivation in mosaic tissues) → 2) Localized hyperactivation of RAS-MAPK signaling in a subset of embryonic lineages → 3) Abnormal development of neural-crest/mesenchyme-derived tissues (skin adnexa/subcutis, ocular surface/choristomas, meninges/cranial vessels, brain malformations, lipomas/cysts) → 4) Clinical triad of cutaneous, ocular, and CNS abnormalities; in some, secondary complications such as epilepsy, hydrocephalus, and tumor predisposition. (bennett2016mosaicactivatingmutations pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 7-8, ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3)

6.2 Candidate pathway/ontology terms (suggested)

7. Anatomical structures affected

ECCL predominantly affects: - Skin/scalp and craniofacial subcutis (nevus psiloliparus; subcutaneous lipomas; alopecia/aplasia). (moog2009encephalocraniocutaneouslipomatosis pages 1-2) - Eye/adnexa (epibulbar/limbal dermoids/lipodermoids; choristomas). (moog2009encephalocraniocutaneouslipomatosis pages 4-4) - CNS and meninges (intracranial/spinal lipomas; arachnoid cysts; hemispheric atrophy; porencephalic cysts; cortical dysplasia/calcification patterns). (moog2009encephalocraniocutaneouslipomatosis pages 5-6, siddiqui2017encephalocraniocutaneouslipomatosisa pages 2-5)

Lateralization: although often unilateral/asymmetric, bilateral skin/eye involvement occurs in ~40% of Moog’s 54-case synthesis. (moog2009encephalocraniocutaneouslipomatosis pages 5-6)

8. Temporal development

8.1 Onset

Most characteristic lesions are congenital/present at birth (scalp/ocular/cerebral malformations). (moog2009encephalocraniocutaneouslipomatosis pages 1-2, siddiqui2017encephalocraniocutaneouslipomatosisa pages 1-2)

8.2 Progression

ECCL is often described as non-progressive/static, but selected features may emerge or progress (e.g., certain vascular lesions, hydrocephalus; progressive jaw/bone lesions in some). (moog2009encephalocraniocutaneouslipomatosis pages 7-8, moog2009encephalocraniocutaneouslipomatosis pages 5-6)

8.3 Seizure timing

Among reported seizure cases in Moog’s synthesis, many began in infancy (9 within first month; 7 within first year). (moog2009encephalocraniocutaneouslipomatosis pages 5-6)

9. Inheritance and population

9.1 Inheritance pattern

ECCL is predominantly sporadic with no reported recurrence in siblings/offspring in Moog’s review, supporting a postzygotic mosaic mechanism rather than Mendelian inheritance. (moog2009encephalocraniocutaneouslipomatosis pages 7-8)

9.2 Epidemiology

  • Moog’s review included 54 cases (32 male; 22 female). (moog2009encephalocraniocutaneouslipomatosis pages 7-8)
  • Later reviews cited <80 cases, including a literature search identifying 77 patients. (garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 1-2)

Prevalence/incidence: Not available in retrieved evidence; no population-based estimates were found.

10. Diagnostics

10.1 Clinical criteria

Moog (2009) revised diagnostic criteria (Box 1) define major/minor features across eye, skin, CNS, and other findings; examples include ocular choristoma and proven nevus psiloliparus (major) and multiple CNS imaging features (minor) such as arachnoid cysts, hemispheric atrophy, porencephalic cysts, asymmetric ventricles/hydrocephalus, and calcifications (not basal ganglia). (moog2009encephalocraniocutaneouslipomatosis pages 6-7, moog2009encephalocraniocutaneouslipomatosis media 02ca15fc)

10.2 Imaging

Neuroimaging commonly identifies intracranial/spinal lipomas, arachnoid and porencephalic cysts, hemispheric atrophy, and calcifications; these findings also guide differential diagnosis (e.g., Sturge–Weber syndrome, hemimegalencephaly). (siddiqui2017encephalocraniocutaneouslipomatosisa pages 2-5)

10.3 Genetic testing strategy (mosaic disease)

Because variants can be absent in blood, diagnostic yield is improved by sequencing affected tissue (e.g., scalp lesion fibroblasts, lipoma, brain/tumor tissue) with high-depth approaches and/or sensitive mosaic detection such as ddPCR. (kordacka2019sensitivedetectionof pages 1-2, venigalla2025histopathologicfeaturesand pages 5-7)

11. Outcome / prognosis

Outcomes vary widely. In Moog’s synthesis, about two-thirds had normal development or mild delay; seizures were present in ~half, with a subset refractory. (moog2009encephalocraniocutaneouslipomatosis pages 5-6, moog2009encephalocraniocutaneouslipomatosis pages 7-8)

12. Treatment

There is no disease-specific curative treatment; management is symptom-directed and multidisciplinary. (siddiqui2017encephalocraniocutaneouslipomatosisa pages 5-5, karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5)

Examples of real-world implementations (from recent case literature): - Drug-refractory epilepsy: A child with ECCL failed multiple antiseizure medications (levetiracetam, zonisamide, valproate, clobazam) and underwent functional hemispherectomy, achieving Engel class IA seizure freedom at 2.5 years with functional and neuropsychological improvements. (koueik2025functionalhemispherectomyfor pages 2-3) - Hydrocephalus: ventriculoperitoneal shunting may be required in some cases. (karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5) - Ocular complications: topical timolol for secondary glaucoma; temporary tarsorrhaphy for lagophthalmos in an infant managed conservatively with serial MRI. (subbiah2022encephalocraniocutaneouslipomatosisa pages 1-2) - Targeted therapy (tumor-associated): In a child with progressive pilocytic astrocytoma and mosaic activating FGFR1 p.Lys656Glu, off-label trametinib (MEK inhibitor) was associated with stable tumor size at 6 months after multiple chemotherapy regimens. (bavle2018encephalocraniocutaneouslipomatosis. pages 1-2)

Clinical trials: A ClinicalTrials.gov query retrieved no ECCL-specific interventional trials; the returned trials were unrelated false matches. (clinical trial search state; no relevant trial context IDs available)

13. Prevention

Primary prevention is not currently feasible because ECCL is a sporadic postzygotic mosaic developmental disorder. Secondary/tertiary prevention is implemented as surveillance and early management of complications (seizures, hydrocephalus, spinal cord compression, tumor monitoring where indicated). (karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5, koueik2025functionalhemispherectomyfor pages 2-3)

14. Other species / natural disease

No naturally occurring non-human ECCL analogs were identified in retrieved sources.

15. Model organisms

No ECCL-specific animal models, iPSC-derived models, or organoid models were identified in retrieved sources. Experimental evidence includes patient-derived fibroblast cell lines used for functional signaling studies demonstrating activated FGFR/RAS-MAPK signaling. (bennett2016mosaicactivatingmutations pages 1-2)

Expert opinion / synthesis (authoritative perspectives)

Artifacts (structured summaries)

Table (click to expand)
Identifier type Value Source Notes
Disease name Encephalocraniocutaneous lipomatosis (ECCL) Machnikowska-Sokołowska et al., 2022; Moog, 2009 (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 1-2) Rare sporadic neurocutaneous disorder; common abbreviation ECCL.
OMIM #613001 Machnikowska-Sokołowska et al., 2022 (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2) Explicitly stated in retrieved source.
Orphanet ORPHA:2396 Marechal et al., 2024 preprint (marechal2024brafmutantschwanncells pages 1-4) Explicitly stated in retrieved source; preprint rather than peer-reviewed disease database paper.
Synonym Haberland syndrome Siddiqui et al., 2017; Garozzo et al., 2018; Moog, 2009 (siddiqui2017encephalocraniocutaneouslipomatosisa pages 1-2, garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 1-2) Common eponymous synonym used across reviews/case reports.
Synonym Fishman syndrome / Fishman’s syndrome Siddiqui et al., 2017; Garozzo et al., 2018; Moog, 2009 (siddiqui2017encephalocraniocutaneouslipomatosisa pages 1-2, garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 1-2) Alternate historical synonym.
MONDO ID Not found in retrieved sources Retrieved literature only (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4) Should be verified directly in MONDO/OBO resource.
MeSH Not found in retrieved sources Retrieved literature only (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4) Should be verified directly in MeSH.
ICD-10 Not found in retrieved sources Retrieved literature only (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4) No explicit ICD-10 code identified in retrieved sources.
ICD-11 Not found in retrieved sources Retrieved literature only (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4) No explicit ICD-11 code identified in retrieved sources.

Table: This table summarizes the key disease identifiers and synonyms for encephalocraniocutaneous lipomatosis (ECCL) that were explicitly available in the retrieved sources. It is useful for standardizing nomenclature before populating a disease knowledge base entry.

Table (click to expand)
Gene/pathway Variant examples (HGVS protein and c.) Evidence type/tissue and mosaicism Mechanistic interpretation Key citation
FGFR1 p.Asn546Lys / c.1638C>A; p.Lys656Glu / c.1966A>G Primary human genetic evidence from affected tissues in ECCL; postzygotic mosaic activating variants detected by exome/targeted resequencing, with low-level/variable allele fractions across lesional tissues and often absent from blood/saliva; hotspot variants also identified in cultured skin/lesional tissue (bennett2016mosaicactivatingmutations pages 1-2, venigalla2025histopathologicfeaturesand pages 5-7) Canonical activating FGFR1 kinase-domain variants. Bennett et al. showed increased phosphorylated FGFRs and FRS2 with constitutive downstream signaling, supporting RAS-MAPK pathway activation as a core ECCL mechanism; explains mosaic neurocutaneous malformation phenotype and overlap with mosaic RASopathies (bennett2016mosaicactivatingmutations pages 1-2, venigalla2025histopathologicfeaturesand pages 5-7) Bennett 2016; Kordacka 2019 (bennett2016mosaicactivatingmutations pages 1-2, venigalla2025histopathologicfeaturesand pages 5-7)
FGFR1 p.Asn546Lys / c.1638C>A (reported as N546K) Human case report with coexisting pilocytic astrocytoma; mutation detected in ECCL patient, with ddPCR demonstrating differential low-level mosaic distribution across affected and unaffected tissues, highlighting diagnostic utility of highly sensitive assays for mosaicism (bennett2016mosaicactivatingmutations pages 1-2) Supports FGFR1 N546K as a plausible causative ECCL variant and reinforces that mosaic distribution can extend beyond overt lesions; also supports link between ECCL molecular etiology and brain tumor predisposition (bennett2016mosaicactivatingmutations pages 1-2) Kordacka 2019; Bennett 2016 background (bennett2016mosaicactivatingmutations pages 1-2)
KRAS Codon 146 hotspot variants (exact nucleotide/protein change not specified in retrieved 2024 excerpt) Human clinical/tumor-associated evidence; Ferraciolli 2024 describes ECCL as a sporadic RASopathy and reports a KRAS codon 146 mutation in an ECCL patient with diffuse leptomeningeal glioneural tumor; broader retrieved literature places codon 146 KRAS variants within mosaic neurocutaneous/RASopathy spectrum overlapping ECCL and related disorders (ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3) Alternative postzygotic activator converging on RAS-MAPK signaling; supports molecular heterogeneity of ECCL and a continuum with other mosaic RASopathies rather than a single-gene disorder (ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3) Ferraciolli 2024 (ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3)
NF1 / RAS-MAPK Germline p.Ser1745 / c.5234C>G plus somatic second hit p.Arg1306 / c.3916C>T on different alleles Human molecular pathology evidence from blood, cerebral tissue, and jaw giant cell lesions; early embryonic mosaic biallelic NF1 inactivation (Happle type 2 / second-hit mosaicism) demonstrated in affected tissues, not explained by FGFR1/KRAS alone (smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 1-6) Alternate mechanism for ECCL phenotype: not activating FGFR1/KRAS directly, but producing localized severe RAS-MAPK upregulation through loss of neurofibromin. Expands ECCL etiologic spectrum to convergent pathway dysregulation from different mosaic events (smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 1-6) Smeijers 2024 (smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 1-6)
RAS-MAPK pathway (downstream convergence) Not a single variant; pathway-level convergence downstream of FGFR1/KRAS and via NF1 loss Functional assay evidence plus clinicogenetic convergence across human cases: FGFR1 activating variants increase receptor phosphorylation/signaling; ECCL-associated mechanisms from FGFR1, KRAS, and NF1 all point to embryonic mosaic dysregulation of the same pathway (bennett2016mosaicactivatingmutations pages 1-2, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 1-6) Best current model: ECCL is a mosaic developmental RASopathy in which early postzygotic alterations in cranial/neural crest–related lineages cause ocular, cutaneous, and CNS malformations; tumor predisposition likely reflects the oncogenic nature of the same pathway lesions (bennett2016mosaicactivatingmutations pages 1-2, ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13) Bennett 2016; Ferraciolli 2024; Smeijers 2024 (bennett2016mosaicactivatingmutations pages 1-2, ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3, smeijers2024encephalocraniocutaneouslipomatosisphenotype pages 9-13)

Table: This table summarizes the main genetic mechanisms currently linked to encephalocraniocutaneous lipomatosis, emphasizing mosaic FGFR1 activation, KRAS codon 146 involvement, and convergent NF1-associated RAS-MAPK dysregulation. It is useful for quickly mapping reported variants, tissue evidence, and mechanistic interpretation for knowledge-base curation.

Table (click to expand)
Domain Phenotype (plain language) Frequency/statistic Suggested HPO term(s) Notes (laterality/onset)
Skin Nevus psiloliparus (hairless fatty scalp nevus) 44/54 in Moog 2009; ~80% in Bennett 2016 HP:0010747 Nevus psiloliparus; HP:0001596 Alopecia Congenital hallmark lesion; often scalp/frontotemporal; may support definite/probable diagnosis depending on associated criteria (moog2009encephalocraniocutaneouslipomatosis pages 1-2, bennett2016mosaicactivatingmutations pages 1-2)
Skin Subcutaneous fatty masses (frontotemporal/zygomatic region) 21/54 HP:0001001 Abnormality of the skin; HP:0012052 Subcutaneous lipoma Typically craniofacial/frontotemporal; usually congenital and often asymmetric (moog2009encephalocraniocutaneouslipomatosis pages 1-2)
Skin Scarring alopecia from focal scalp aplasia 14/54 HP:0200024 Scarring alopecia; HP:0001067 Aplasia cutis congenita Present from birth/early infancy; may coexist with non-scarring alopecia patches (moog2009encephalocraniocutaneouslipomatosis pages 1-2)
Skin/Eye patterning Bilateral skin and/or eye abnormalities 22/54 (40%) HP:0012832 Bilateral; HP:0000621 Abnormality of the eye; HP:0001574 Abnormality of the integument Although ECCL is often asymmetric/unilateral, bilateral involvement is well documented (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Eye Ocular choristomas / epibulbar or limbal dermoids / lipodermoids 43/54 in Moog review; ~80% ocular choristomas in Bennett 2016 HP:0100012 Epibulbar dermoid; HP:0001140 Ocular choristoma Can be unilateral or bilateral; among the most characteristic ocular findings (bennett2016mosaicactivatingmutations pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 4-4)
CNS imaging Lipomas on neuroimaging (overall) 33/54 HP:0012032 Intracranial lipoma; HP:0009721 Spinal lipoma Lipomas were the most prominent neuroimaging feature in the review cohort (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
CNS imaging Intracranial lipomas 31/54; cerebellopontine angle in 19/31 HP:0012032 Intracranial lipoma Frequent posterior fossa/CPA involvement; generally congenital, often ipsilateral to cutaneous/ocular findings (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
CNS imaging Intraspinal/spinal lipomas 12/14 when specifically investigated; ~61% intracranial and intraspinal lipomas in Bennett 2016 HP:0009721 Spinal lipoma Spinal MRI is recommended when ECCL is suspected because lesions are common when looked for and may be extensive (moog2009encephalocraniocutaneouslipomatosis pages 5-6, bennett2016mosaicactivatingmutations pages 1-2)
CNS imaging Arachnoid cysts 21 cases HP:0006721 Arachnoid cyst Minor CNS criterion in Moog framework; contributes to asymmetric congenital brain malformation pattern (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Neurology Seizures / epilepsy 27/54 had seizures; onset among seizure cases: 9 in first month, 7 within first year, 6 after first year; 24/54 not reported HP:0001250 Seizure; HP:0002373 Febrile seizures not specified / use broad seizure term About half of reported patients affected; response among 27 seizure cases: 8 refractory, 6 difficult to treat, 13 responded well to medication (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Neurodevelopment Developmental outcome distribution Among 45 with data: 13 normal, 16 mild delay, 16 moderate-severe/unspecified delay HP:0011344 Intellectual disability, mild; HP:0001249 Intellectual disability; HP:0001263 Global developmental delay Roughly two-thirds had normal development or only mild delay; severity did not clearly track extent of CNS malformations (moog2009encephalocraniocutaneouslipomatosis pages 1-2, moog2009encephalocraniocutaneouslipomatosis pages 5-6)

Table: This table compiles the best-available quantitative phenotype data for encephalocraniocutaneous lipomatosis from the 54-patient Moog 2009 review, with Bennett 2016 estimates added where available. It is useful for rapid knowledge-base curation of core clinical features, frequencies, laterality, and suggested HPO mappings.

Table (click to expand)
Area Key points Real-world implementation examples Suggested ontology terms (MAXO/LOINC/RadLex as applicable) Key citations
Clinical diagnostic criteria Diagnosis is primarily clinical and syndromic using Moog 2009 revised criteria (Box 1): major/minor findings across eye, skin, CNS, and other systems; major examples include ocular choristoma, proven nevus psiloliparus, intracranial lipoma, and intraspinal lipoma. Definite diagnosis generally requires multi-system involvement with sufficient major criteria; strict criteria were recommended pending molecular clarification. Use structured assessment of ocular choristoma/dermoid, scalp nevus psiloliparus or patchy alopecia, and CNS lipoma/cyst/atrophy pattern at first specialist evaluation. MAXO: clinical examination; RadLex: MRI brain, MRI spine, CT head; LOINC: not disease-specific (moog2009encephalocraniocutaneouslipomatosis pages 6-7, siddiqui2017encephalocraniocutaneouslipomatosisa pages 2-5, moog2009encephalocraniocutaneouslipomatosis media 02ca15fc)
Neuroimaging workup Characteristic imaging findings include intracranial lipomas, intraspinal lipomas, arachnoid cysts, porencephalic cysts, hemispheric atrophy, ventricular asymmetry/hydrocephalus, leptomeningeal angiomatosis, dysplastic cortex, and non-basal-ganglia calcifications. MRI is preferred for brain/spine malformations; CT can better show calcifications. Brain MRI at diagnosis; spine MRI when ECCL is suspected because spinal lipomas are common when specifically investigated; CT used when cortical calcification pattern needs clarification. MAXO: MRI surveillance; RadLex: MRI brain, MRI spine, CT head (siddiqui2017encephalocraniocutaneouslipomatosisa pages 2-5, moog2009encephalocraniocutaneouslipomatosis pages 5-6, karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5, garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 4-5)
Molecular diagnosis Mosaic disease biology means blood/saliva may be negative. Highest-yield testing uses affected tissue (eg, scalp lesion/nevus psiloliparus fibroblasts, lipoma, brain or tumor tissue) with high-depth sequencing; recurrent FGFR1 variants include p.Asn546Lys and p.Lys656Glu, and KRAS codon 146 variants are established in the ECCL spectrum. ddPCR and other sensitive methods improve low-level mosaic detection. Sequence affected tissue rather than relying only on blood; ddPCR detected FGFR1 N546K mosaicism across tissues in a patient with ECCL and pilocytic astrocytoma. MAXO: genetic testing; LOINC: molecular genetics study; RadLex: image-guided biopsy if needed (kordacka2019sensitivedetectionof pages 1-2, bennett2016mosaicactivatingmutations pages 1-2, venigalla2025histopathologicfeaturesand pages 5-7, garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 4-5)
Multidisciplinary surveillance Ongoing care should involve ophthalmology, dermatology, neurology/neurosurgery, radiology, neurodevelopmental/rehabilitation services, and musculoskeletal assessment. Surveillance is recommended because ECCL can be associated with epilepsy, hydrocephalus, spinal cord compression, and tumor predisposition. Multisystem evaluation after diagnosis; serial developmental follow-up and repeat brain/spine imaging when clinically indicated; literature recommends close clinical and radiologic follow-up. MAXO: multidisciplinary care; MAXO: MRI surveillance; MAXO: neurodevelopmental assessment (koueik2025functionalhemispherectomyfor pages 2-3, koueik2025functionalhemispherectomyfor pages 3-5, karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5, ferraciolli2024haberlandsyndrome(encephalocraniocutaneous pages 1-3)
Antiseizure therapy There is no disease-specific drug therapy for ECCL; seizure treatment is symptomatic. About half of patients have seizures, with a subset having refractory epilepsy. Reported antiseizure medications include levetiracetam, zonisamide, valproate, and clobazam in a child later treated surgically for drug-refractory epilepsy. MAXO: antiseizure medication therapy (koueik2025functionalhemispherectomyfor pages 2-3, siddiqui2017encephalocraniocutaneouslipomatosisa pages 5-5, moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Hydrocephalus management Hydrocephalus occurs in a substantial minority; some patients require neurosurgical CSF diversion. Ventriculoperitoneal shunt placement is specifically recommended/used for symptomatic hydrocephalus in case-based literature. MAXO: neurosurgical shunt procedure (karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5, siddiqui2017encephalocraniocutaneouslipomatosisa pages 2-5)
Spinal lipoma management Spinal lipomas are common when sought and may cause tethered cord or compression; treatment is symptom-driven. Debulking of spinal lipomas is described for cord compression/tethered cord symptoms. MAXO: surgical debulking; MAXO: spinal surgery (karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5, moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Conservative monitoring Many lesions are static, so watchful waiting with serial imaging is appropriate when surgery risks outweigh benefit. In an infant with enlarging orbital/retrobulbar dermoids and intracranial lipomas, a multidisciplinary team chose close monitoring with serial MRIs and reserved surgery for airway compression or neurologic deficits. MAXO: MRI surveillance; MAXO: expectant management (subbiah2022encephalocraniocutaneouslipomatosisa pages 1-2)
Ocular symptomatic management Ocular disease can include choristomas/dermoids, secondary glaucoma, exposure symptoms, and progressive surface compromise; management is individualized. Topical timolol was used for secondary glaucoma; temporary tarsorrhaphy was used for lagophthalmos in an ECCL infant. MAXO: ophthalmic drug therapy; MAXO: tarsorrhaphy; MAXO: glaucoma management (subbiah2022encephalocraniocutaneouslipomatosisa pages 1-2)
Cosmetic / lesion-directed surgery Cutaneous and ocular lesions may be surgically corrected for symptoms or cosmesis; surgery is individualized because some lesions are extensive and non-urgent. Surgical correction of ocular or cutaneous lesions is described in reviews/case reports; cosmetic improvement is a typical indication. MAXO: surgical excision; MAXO: reconstructive surgery (siddiqui2017encephalocraniocutaneouslipomatosisa pages 5-5, karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5)
Epilepsy surgery For unilateral hemispheric drug-refractory epilepsy with concordant presurgical data, hemispherectomy/hemispheric disconnection is feasible. A 5-year-old with ECCL underwent left peri-insular functional hemispherectomy after failed medications; she was seizure free (Engel class IA) at 2.5 years, ambulatory with orthotic assistance by 3 months, and had neuropsychological improvement at 1.5 years. MAXO: hemispherectomy; MAXO: epilepsy surgery; RadLex: video-EEG, fMRI, PET-MRI (koueik2025functionalhemispherectomyfor pages 2-3, koueik2025functionalhemispherectomyfor pages 1-2, koueik2025functionalhemispherectomyfor pages 5-6)
Targeted therapy / tumor management ECCL is a mosaic RAS/MAPK-pathway disorder and tumor predisposition syndrome; targeted therapy evidence is limited to case reports. In a child with progressive pilocytic astrocytoma and mosaic FGFR1 p.Lys656Glu, off-label trametinib (MEK inhibitor) was started after progression on vinblastine, carboplatin/vincristine, and irinotecan/bevacizumab, with stable tumor size at 6 months. MAXO: targeted small-molecule therapy; MAXO: MEK inhibitor therapy (bavle2018encephalocraniocutaneouslipomatosis. pages 1-2)

Table: This table summarizes the best-supported diagnostic and management practices for encephalocraniocutaneous lipomatosis, including Moog diagnostic criteria, imaging, mosaic genetic testing, surveillance, and reported real-world treatments. It is useful for translating case-series and primary literature into structured knowledge-base entries with ontology-ready actions.

Key figures/tables from retrieved literature

Moog 2009 revised diagnostic criteria (Box 1) were retrieved as an image crop. (moog2009encephalocraniocutaneouslipomatosis media 02ca15fc)

Reference metadata (publication dates and URLs from retrieved sources)

Requested items not available in retrieved evidence (transparent gaps)

  • MONDO ID, MeSH identifier, ICD-10/ICD-11 codes: not explicitly present in tool-retrieved full texts. (machnikowskasokołowska2022encephalocraniocutaneouslipomatosisa pages 1-2, marechal2024brafmutantschwanncells pages 1-4)
  • Population prevalence/incidence and quantitative malignancy risk estimates: not found in retrieved evidence (case-based literature predominates). (moog2009encephalocraniocutaneouslipomatosis pages 7-8, garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 1-2)

References

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  25. (koueik2025functionalhemispherectomyfor pages 1-2): Joyce Koueik, David Hsu, Jeffrey Helgager, and Raheel Ahmed. Functional hemispherectomy for seizure control in encephalocraniocutaneous lipomatosis: illustrative case. Journal of Neurosurgery: Case Lessons, Apr 2025. URL: https://doi.org/10.3171/case2578, doi:10.3171/case2578. This article has 0 citations.

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