Encephalocraniocutaneous lipomatosis (ECCL, Haberland syndrome) is a rare congenital neurocutaneous disorder caused by postzygotic (somatic) gain-of-function mutations in FGFR1 or KRAS. It is characterized by unilateral ocular, cutaneous, and central nervous system anomalies. Key clinical features include hairless fatty tissue nevus of the scalp (nevus psiloliparus), choristoma of the eye, and intraspinal and intracerebral lipomas. As a mosaic disorder, it is not typically inherited in a Mendelian pattern. Patients with FGFR1-associated ECCL carry a risk of developing malignant brain tumors.
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name: Encephalocraniocutaneous Lipomatosis
creation_date: '2026-04-04T12:00:00Z'
updated_date: '2026-05-08T23:53:01Z'
category: Genetic
description: >-
Encephalocraniocutaneous lipomatosis (ECCL, Haberland syndrome) is a rare congenital
neurocutaneous disorder caused by postzygotic (somatic) gain-of-function mutations
in
FGFR1 or KRAS. It is characterized by unilateral ocular, cutaneous, and central
nervous
system anomalies. Key clinical features include hairless fatty tissue nevus of the
scalp
(nevus psiloliparus), choristoma of the eye, and intraspinal and intracerebral lipomas.
As a mosaic disorder, it is not typically inherited in a Mendelian pattern. Patients
with FGFR1-associated ECCL carry a risk of developing malignant brain tumors.
disease_term:
preferred_term: encephalocraniocutaneous lipomatosis
term:
id: MONDO:0013074
label: encephalocraniocutaneous lipomatosis
parents:
- FGFR1-related disorder
- Neurocutaneous disorder
inheritance:
- name: Somatic mosaic
inheritance_term:
preferred_term: Somatic mosaicism
term:
id: HP:0001442
label: Typified by somatic mosaicism
description: >-
ECCL is caused by postzygotic somatic mutations, resulting in mosaic distribution
of the activating FGFR1 variant. It is not typically inherited from parents.
evidence:
- reference: PMID:34547955
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "ECCL was confirmed by the identification of a postzygotic FGFR1 mutation."
explanation: Confirms postzygotic (somatic mosaic) origin of the FGFR1 mutation in ECCL.
pathophysiology:
- name: Somatic FGFR1 gain-of-function in developing tissues
description: >-
Postzygotic activating mutations in FGFR1 occur during early embryonic development,
leading to mosaic overactivation of FGFR1 signaling in affected tissues. This
drives aberrant proliferation of mesenchymal and neural crest-derived cells,
producing lipomas, cutaneous hamartomas, and CNS anomalies in a mosaic
distribution. ECCL shares significant phenotypic overlap with mosaic RASopathies
due to convergent activation of the RAS-MAPK pathway.
gene:
preferred_term: FGFR1
description: Fibroblast growth factor receptor 1, somatically activated by gain-of-function mutations in ECCL.
modifier: INCREASED
term:
id: hgnc:3688
label: FGFR1
biological_processes:
- preferred_term: FGFR signaling pathway
term:
id: GO:0008543
label: fibroblast growth factor receptor signaling pathway
modifier: INCREASED
evidence:
- reference: PMID:37486073
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder caused by somatic FGFR1 and KRAS variants."
explanation: Confirms somatic FGFR1 variants as a cause of ECCL.
phenotypes:
- name: Intracranial lipomas
description: >-
Intracerebral and intraspinal lipomas are characteristic CNS manifestations.
They may cause ventriculomegaly and cerebral atrophy.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Midline central nervous system lipomas
term:
id: HP:0006866
label: Midline central nervous system lipomas
evidence:
- reference: PMID:34547955
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Key clinical features include hairless fatty tissue nevus of the scalp, choristoma of the eye and intraspinal and intracerebral lipomas."
explanation: Intracerebral and intraspinal lipomas are listed as key clinical features.
- name: Cutaneous lipomas and nevi
description: >-
Hairless fatty tissue nevus of the scalp (nevus psiloliparus) and facial
hamartomas are characteristic cutaneous features, typically unilateral.
frequency: OBLIGATE
phenotype_term:
preferred_term: Epidermal nevus
term:
id: HP:0010816
label: Epidermal nevus
evidence:
- reference: PMID:34547955
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "It is characterized by unilateral ocular, cutaneous and central nervous system anomalies."
explanation: Unilateral cutaneous anomalies are a defining feature of ECCL.
- name: Ocular choristoma
description: >-
Choristoma (dermoid or lipodermoid) of the eye, typically epibulbar, is a
key diagnostic feature of ECCL. Limbal dermoids are the most common ocular
manifestation.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Ocular choristoma (limbal dermoid)
term:
id: HP:0001140
label: Limbal dermoid
evidence:
- reference: PMID:34547955
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Key clinical features include hairless fatty tissue nevus of the scalp, choristoma of the eye and intraspinal and intracerebral lipomas."
explanation: Choristoma of the eye is listed as a key clinical feature of ECCL.
- name: Ventriculomegaly
description: Cerebral ventriculomegaly with possible cerebral atrophy.
frequency: FREQUENT
phenotype_term:
preferred_term: Ventriculomegaly
term:
id: HP:0002119
label: Ventriculomegaly
evidence:
- reference: PMID:34547955
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Prenatal ultrasound and MRI of the third trimester showed multifocal spinal lesions and left lateral cerebral ventriculomegaly with cerebral atrophy."
explanation: Ventriculomegaly demonstrated on prenatal imaging in an ECCL case.
genetic:
- name: Somatic FGFR1 gain-of-function mutations
association: Causative
gene_term:
preferred_term: FGFR1
term:
id: hgnc:3688
label: FGFR1
notes: >-
Postzygotic somatic activating mutations in FGFR1 (e.g., p.K656E) cause ECCL.
Somatic KRAS variants can also cause ECCL. Genetic testing of affected tissue
(not blood) is typically required for molecular diagnosis. Patients with
FGFR1-associated ECCL carry a risk of developing malignant brain tumors.
variants:
- name: p.K656E
description: Activating missense variant in the kinase domain of FGFR1 identified in affected tissue.
clinical_significance: PATHOGENIC
evidence:
- reference: PMID:37486073
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "next-generation sequencing of affected tissue identified a pathologic FGFR1 p.K656E variant, thereby establishing a molecular diagnosis."
explanation: Identifies p.K656E as a pathogenic FGFR1 variant in ECCL.
treatments:
- name: Neurosurgical management
description: >-
Surgical management of intracranial lipomas and associated complications
such as hydrocephalus or mass effect.
treatment_term:
preferred_term: Neurosurgery
term:
id: MAXO:0000004
label: surgical procedure
- name: Brain tumor surveillance
description: >-
Patients with FGFR1-associated ECCL carry a risk of developing malignant
brain tumors, necessitating regular neuroimaging surveillance.
treatment_term:
preferred_term: Brain tumor surveillance
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:37486073
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Patients with FGFR1-associated ECCL carry a risk of developing malignant brain tumors; thus, genetic testing of patients with suspected ECCL has important management implications."
explanation: Establishes the need for brain tumor surveillance in FGFR1-associated ECCL.
references:
- reference: DOI:10.1002/ajmg.a.61256
title: Sensitive detection of <i>FGFR1 N546K</i> mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide.
supporting_text: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide.
evidence:
- reference: DOI:10.1002/ajmg.a.61256
reference_title: Sensitive detection of <i>FGFR1 N546K</i> mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.1007/s00062-024-01389-0
title: Haberland Syndrome (Encephalocraniocutaneous Lipomatosis) with Development of Diffuse Leptomeningeal Glioneural Tumor (DL-GNT) during Adolescence
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Haberland Syndrome (Encephalocraniocutaneous Lipomatosis) with Development of Diffuse Leptomeningeal Glioneural Tumor (DL-GNT) during Adolescence
supporting_text: Haberland Syndrome (Encephalocraniocutaneous Lipomatosis) with Development of Diffuse Leptomeningeal Glioneural Tumor (DL-GNT) during Adolescence
- reference: DOI:10.1007/s00381-021-05099-7
title: 'Encephalocraniocutaneous lipomatosıs (Haberland syndrome) in a newborn baby: a case report with review of literature'
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: 'Encephalocraniocutaneous lipomatosıs (Haberland syndrome) in a newborn baby: a case report with review of literature'
supporting_text: 'Encephalocraniocutaneous lipomatosıs (Haberland syndrome) in a newborn baby: a case report with review of literature'
- reference: DOI:10.1016/j.ajhg.2016.02.006
title: Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis
supporting_text: Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis
- reference: DOI:10.1055/s-0038-1667004
title: Encephalocraniocutaneous Lipomatosis (Haberland Syndrome or Fishman Syndrome)
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis is a sporadic, congenital neurocutaneous disorder characterized by the involvement of skin, central nervous system, and eye.
supporting_text: Encephalocraniocutaneous lipomatosis is a sporadic, congenital neurocutaneous disorder characterized by the involvement of skin, central nervous system, and eye.
evidence:
- reference: DOI:10.1055/s-0038-1667004
reference_title: Encephalocraniocutaneous Lipomatosis (Haberland Syndrome or Fishman Syndrome)
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Encephalocraniocutaneous lipomatosis is a sporadic, congenital neurocutaneous disorder characterized by the involvement of skin, central nervous system, and eye.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.1097/mph.0000000000001170
title: Encephalocraniocutaneous Lipomatosis
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: A 5-year-old boy presented with worsening headaches for 3 months.
supporting_text: A 5-year-old boy presented with worsening headaches for 3 months.
evidence:
- reference: DOI:10.1097/mph.0000000000001170
reference_title: Encephalocraniocutaneous Lipomatosis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: A 5-year-old boy presented with worsening headaches for 3 months.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.1101/2024.04.24.590951
title: Oncogenic MAPK pathway activation disrupts Schwann cell fate commitment, inducing congenital and progressive neuropathy in mice
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: RASopathies, rare congenital syndromes affecting multiple organ systems, often include peripheral neuropathy of unknown origin.
supporting_text: RASopathies, rare congenital syndromes affecting multiple organ systems, often include peripheral neuropathy of unknown origin.
evidence:
- reference: DOI:10.1101/2024.04.24.590951
reference_title: Oncogenic MAPK pathway activation disrupts Schwann cell fate commitment, inducing congenital and progressive neuropathy in mice
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: RASopathies, rare congenital syndromes affecting multiple organ systems, often include peripheral neuropathy of unknown origin.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.1136/jmg-2023-109785
title: Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in the <i>NF1</i> gene
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement.
supporting_text: Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement.
evidence:
- reference: DOI:10.1136/jmg-2023-109785
reference_title: Encephalocraniocutaneous lipomatosis phenotype associated with mosaic biallelic pathogenic variants in the <i>NF1</i> gene
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic congenital condition characterised by ocular, cutaneous and central nervous system involvement.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.1177/1971400917693638
title: 'Encephalocraniocutaneous lipomatosis: A case report with review of literature'
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome is an uncommon sporadic neurocutaneous syndrome of unknown origin.
supporting_text: Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome is an uncommon sporadic neurocutaneous syndrome of unknown origin.
evidence:
- reference: DOI:10.1177/1971400917693638
reference_title: 'Encephalocraniocutaneous lipomatosis: A case report with review of literature'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome is an uncommon sporadic neurocutaneous syndrome of unknown origin.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.3171/case2578
title: 'Functional hemispherectomy for seizure control in encephalocraniocutaneous lipomatosis: illustrative case'
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome composed of a spectrum of congenital cutaneous, ocular, and brain anomalies.
supporting_text: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome composed of a spectrum of congenital cutaneous, ocular, and brain anomalies.
evidence:
- reference: DOI:10.3171/case2578
reference_title: 'Functional hemispherectomy for seizure control in encephalocraniocutaneous lipomatosis: illustrative case'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome composed of a spectrum of congenital cutaneous, ocular, and brain anomalies.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.3390/brainsci12121641
title: 'Encephalocraniocutaneous Lipomatosis, a Radiological Challenge: Two Atypical Case Reports and Literature Review'
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: 'Encephalocraniocutaneous lipomatosis (ECCL; Haberland syndrome, #613001) is an extremely rare congenital disorder that is manifested by the involvement of the skin, eyes and central nervous system (CNS).'
supporting_text: 'Encephalocraniocutaneous lipomatosis (ECCL; Haberland syndrome, #613001) is an extremely rare congenital disorder that is manifested by the involvement of the skin, eyes and central nervous system (CNS).'
evidence:
- reference: DOI:10.3390/brainsci12121641
reference_title: 'Encephalocraniocutaneous Lipomatosis, a Radiological Challenge: Two Atypical Case Reports and Literature Review'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 'Encephalocraniocutaneous lipomatosis (ECCL; Haberland syndrome, #613001) is an extremely rare congenital disorder that is manifested by the involvement of the skin, eyes and central nervous system (CNS).'
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.3390/dermatopathology12040039
title: Histopathologic Features and Molecular Markers of Encephalocraniocutaneous Lipomatosis (ECCL)
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations.
supporting_text: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations.
evidence:
- reference: DOI:10.3390/dermatopathology12040039
reference_title: Histopathologic Features and Molecular Markers of Encephalocraniocutaneous Lipomatosis (ECCL)
supports: SUPPORT
evidence_source: OTHER
snippet: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
- reference: DOI:10.7759/cureus.32498
title: 'Encephalocraniocutaneous Lipomatosis: A Case Report and Literature Review'
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: 'Encephalocraniocutaneous Lipomatosis: A Case Report and Literature Review'
supporting_text: 'Encephalocraniocutaneous Lipomatosis: A Case Report and Literature Review'
- reference: DOI:10.1136/jmg.2009.066068
title: Encephalocraniocutaneous lipomatosis
found_in:
- Encephalocraniocutaneous_Lipomatosis-deep-research-falcon.md
findings:
- statement: 54 patients with ECCL were reviewed.
supporting_text: 54 patients with ECCL were reviewed.
evidence:
- reference: DOI:10.1136/jmg.2009.066068
reference_title: Encephalocraniocutaneous lipomatosis
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 54 patients with ECCL were reviewed.
explanation: Deep research cited this publication as relevant literature for Encephalocraniocutaneous Lipomatosis.
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)
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)
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)
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)
Moog (2009) synthesized 54 ECCL cases and provides the most commonly cited quantitative phenotype frequencies in retrieved evidence. (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
Additional frequency estimates (Bennett 2016 excerpt): nevus psiloliparus and ocular choristomas each ~80%; intracranial/intraspinal lipomas ~61%. (bennett2016mosaicactivatingmutations pages 1-2)
Selected HPO mappings are summarized in the phenotype table artifact. (moog2009encephalocraniocutaneouslipomatosis pages 5-6, moog2009encephalocraniocutaneouslipomatosis pages 1-2)
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)
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.
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)
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)
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)
Most characteristic lesions are congenital/present at birth (scalp/ocular/cerebral malformations). (moog2009encephalocraniocutaneouslipomatosis pages 1-2, siddiqui2017encephalocraniocutaneouslipomatosisa pages 1-2)
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)
Among reported seizure cases in Moog’s synthesis, many began in infancy (9 within first month; 7 within first year). (moog2009encephalocraniocutaneouslipomatosis pages 5-6)
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)
Prevalence/incidence: Not available in retrieved evidence; no population-based estimates were found.
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)
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)
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)
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)
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)
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)
No naturally occurring non-human ECCL analogs were identified in retrieved sources.
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)
| 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.
| 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.
| 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.
| 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.
Moog 2009 revised diagnostic criteria (Box 1) were retrieved as an image crop. (moog2009encephalocraniocutaneouslipomatosis media 02ca15fc)
References
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(kordacka2019sensitivedetectionof pages 1-2): Joanna Kordacka, Krzysztof Zakrzewski, Renata Gruszka, Monika Witusik‐Perkowska, Joanna Taha, Beata Sikorska, Paweł P. Liberski, and Magdalena Zakrzewska. Sensitive detection of fgfr1 n546k mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma. American Journal of Medical Genetics Part A, 179:1622-1627, Aug 2019. URL: https://doi.org/10.1002/ajmg.a.61256, doi:10.1002/ajmg.a.61256. This article has 15 citations.
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(garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 1-2): Maria Garozzo, Daniele Attardo, Pierluigi Smilari, Filippo Greco, Agata Fiumara, Agata Polizzi, Concetta Pirrone, Antonio Zanghì, Carmelo Schepis, Francesco Lacarrubba, Giuseppe Micali, Martino Ruggieri, Andrea Praticò, and Marina Mazzurco. Encephalocraniocutaneous lipomatosis (haberland syndrome or fishman syndrome). Journal of Pediatric Neurology, 16:369-378, Aug 2018. URL: https://doi.org/10.1055/s-0038-1667004, doi:10.1055/s-0038-1667004. This article has 2 citations and is from a peer-reviewed journal.
(moog2009encephalocraniocutaneouslipomatosis pages 6-7): U. Moog. Encephalocraniocutaneous lipomatosis. Journal of Medical Genetics, 46:721-729, Jul 2009. URL: https://doi.org/10.1136/jmg.2009.066068, doi:10.1136/jmg.2009.066068. This article has 159 citations and is from a domain leading peer-reviewed journal.
(moog2009encephalocraniocutaneouslipomatosis media 02ca15fc): U. Moog. Encephalocraniocutaneous lipomatosis. Journal of Medical Genetics, 46:721-729, Jul 2009. URL: https://doi.org/10.1136/jmg.2009.066068, doi:10.1136/jmg.2009.066068. This article has 159 citations and is from a domain leading peer-reviewed journal.
(venigalla2025histopathologicfeaturesand pages 5-7): Siddharth Venigalla, Tanvir K. Dhaliwal, Anvita Anumolu, Lena Rafey, Arturo P. Saavedra, and David D. Limbrick. Histopathologic features and molecular markers of encephalocraniocutaneous lipomatosis (eccl). Dermatopathology, 12:39, Nov 2025. URL: https://doi.org/10.3390/dermatopathology12040039, doi:10.3390/dermatopathology12040039. This article has 0 citations.
(siddiqui2017encephalocraniocutaneouslipomatosisa pages 5-5): Shaista Siddiqui, Shazia Naaz, Mehtab Ahmad, Zafar Ahmad Khan, Shagufta Wahab, and Basmah Abdur Rashid. Encephalocraniocutaneous lipomatosis: a case report with review of literature. The Neuroradiology Journal, 30:578-582, Jul 2017. URL: https://doi.org/10.1177/1971400917693638, doi:10.1177/1971400917693638. This article has 10 citations and is from a peer-reviewed journal.
(karaman2021encephalocraniocutaneouslipomatosıs(haberland pages 4-5): Zehra Filiz Karaman and Şerife Ebru Özüdoğru. Encephalocraniocutaneous lipomatosıs (haberland syndrome) in a newborn baby: a case report with review of literature. Child's Nervous System, 37:3951-3955, Mar 2021. URL: https://doi.org/10.1007/s00381-021-05099-7, doi:10.1007/s00381-021-05099-7. This article has 4 citations.
(koueik2025functionalhemispherectomyfor pages 2-3): 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.
(subbiah2022encephalocraniocutaneouslipomatosisa pages 1-2): Deivanai Subbiah, Nur Hafidza Asiff, Norhafizah Hamzah, and Amir Samsudin. Encephalocraniocutaneous lipomatosis: a case report and literature review. Cureus, Dec 2022. URL: https://doi.org/10.7759/cureus.32498, doi:10.7759/cureus.32498. This article has 2 citations.
(bavle2018encephalocraniocutaneouslipomatosis. pages 1-2): Abhishek Bavle, Rikin Shah, Naina Gross, Theresa Gavula, Alejandro Ruiz-Elizalde, Klaas Wierenga, and Rene McNall-Knapp. Encephalocraniocutaneous lipomatosis. Journal of pediatric hematology/oncology, 40 7:553-554, Oct 2018. URL: https://doi.org/10.1097/mph.0000000000001170, doi:10.1097/mph.0000000000001170. This article has 22 citations.
(garozzo2018encephalocraniocutaneouslipomatosis(haberland pages 4-5): Maria Garozzo, Daniele Attardo, Pierluigi Smilari, Filippo Greco, Agata Fiumara, Agata Polizzi, Concetta Pirrone, Antonio Zanghì, Carmelo Schepis, Francesco Lacarrubba, Giuseppe Micali, Martino Ruggieri, Andrea Praticò, and Marina Mazzurco. Encephalocraniocutaneous lipomatosis (haberland syndrome or fishman syndrome). Journal of Pediatric Neurology, 16:369-378, Aug 2018. URL: https://doi.org/10.1055/s-0038-1667004, doi:10.1055/s-0038-1667004. This article has 2 citations and is from a peer-reviewed journal.
(koueik2025functionalhemispherectomyfor pages 3-5): 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.
(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.
(koueik2025functionalhemispherectomyfor pages 5-6): 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.