Encephalocraniocutaneous Lipomatosis Research Articles

Encephalocraniocutaneous Lipomatosis: A Case Report.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome and subclassification of oculoectodermal syndrome. Encephalocraniocutaneous lipomatosis may be associated with postzygotic mutations. However, absence of an identifiable mutation does not preclude a diagnosis of ECCL. Encephalocraniocutaneous lipomatosis commonly causes skin, eye, and central nervous system anomalies. Diagnosis can be made through genetic sequencing or standardized clinical criteria. One clinically apparent major criterion for the diagnosis of ECCL is nevus psiloliparus (NP), a fatty nevus with overlying nonscarring alopecia. In this case, a 50-day-old female infant with uncomplicated birth history presented to dermatology clinic for evaluation of 2 superficial cranial masses that had been present since birth without regression or evolution. One of the masses was located within the hairline and demonstrated overlying nonscarring alopecia, suspicious of NP. Because of concern for ECCL, brain magnetic resonance imaging was ordered and revealed 2 intracranial lipomas. Genetic testing was inconclusive. Excision of the masses was performed at the request of the parents for cosmetic purposes. Histologic evaluation of the surgical specimens confirmed the diagnosis of NP and ECCL. A suspected NP should raise concern for ECCL and prompt further evaluation for systemic involvement. In particular, patients with suspected ECCL should be screened for ocular and CNS involvement. Early identification and diagnosis are important for prognostication because patients with ECCL are at increased risk of developing neoplasms of the head and neck and may require more frequent screening examinations.

Navigating the complexities of encephalocraniocutaneous lipomatosis: a case series and review

IntroductionEncephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome with complex skin, eye, and central nervous system (CNS) symptoms. Diagnosis and treatment are challenging due to its rarity and diverse manifestations. It often involves issues like porencephalic cysts, cortical atrophy, and low-grade gliomas in the CNS, resulting in developmental delays. The spinal cord is frequently affected, leading to problems like medullary compression and radiculopathy, causing back pain and sensory/motor deficits. Surgical interventions are reserved for symptomatic cases to address hydrocephalus or alleviate spinal lipomas. This article reviews a case series to assess surgical risks and neurological outcomes.Case seriesWe present a case series ECCL, focusing on the diffuse lipomatosis of the spinal cord and the intricate surgical procedures involved. A multi-stage surgical approach was adopted, with continuous neuromonitoring employed to safeguard motor pathways. We discuss clinical characteristics, imaging studies, and indications for neurosurgical interventions.DiscussionECCL is a complex syndrome. Diagnosis is challenging and includes clinical evaluation, neuroimaging, and genetic testing. Treatment targets specific symptoms, often requiring surgery for issues like lipomas or cerebral cysts. Surgery involves laminectomies, spinal fusion, and motor pathway monitoring. Thorough follow-up is crucial due to potential CNS complications like low-grade gliomas. Hydrocephalus occurs in some cases, with endoscopic third ventriculostomy (ETV) preferred over ventriculoperitoneal shunt placement.ConclusionNeurosurgery for ECCL is for symptomatic cases. ETV is preferred for hydrocephalus, while the treatment for lipoma is based on the presence of symptoms; the follow-up should assess growth and prevent deformities.

Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies: A Description of a New Imaging Sign

PurposeTo evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of mosaic RASopathy patients. DesignSingle-center retrospective observational study. SubjectsTen eyes with calcified fundus lesions in 7 mosaic RASopathy patients. MethodsThe lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) scan where available. Main Outcome MeasuresThe imaging characteristics of calcified fundus lesions were assessed. ResultsWe found seven patients with mosaic RASopathies, 5 males and 2 females (3 with Linear Sebaceous Nevus Syndrome, 3 with Oculoectodermal Syndrome, and 1 with Encephalocraniocutaneous Lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but two of these lesions involved both the choroid and sclera, with two of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane (CNV) necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan and all four showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, one had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. ConclusionsWe propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas (CaSCCs) and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen.

P221: Clinical features and diagnostic management of infant with encephalocraniocutaneous lipomatosis and congenital hypothyroidism

P221: Clinical features and diagnostic management of infant with encephalocraniocutaneous lipomatosis and congenital hypothyroidism

Encephalocraniocutaneous Lipomatosis, a Radiological Challenge: Two Atypical Case Reports and Literature Review.

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). We report two cases of children with ECCL diagnosis. First was an 8-year-old girl who presented with symptomatic epilepsy, cerebral palsy and developmental delay. In 2020, she was admitted to the hospital due to the exacerbation of paresis and intensified prolonged epileptic seizures, provoked by infection of the middle ear. Diagnostic imaging revealed radiological changes suggestive of ECCL, providing a reason for the diagnosis, despite the lack of skin and eye anomalies. The second child, a 14-year-old girl, was consulted for subtle clinical signs and epilepsy suspicion. Diagnostic imaging findings were similar, though less pronounced. Based on neuroradiological abnormalities typical for Haberland syndrome, the authors discuss possible ECCL diagnosis.

PA01: More than meets the eye: a case of encephalocraniocutaneous lipomatosis

PA01: More than meets the eye: a case of encephalocraniocutaneous lipomatosis

Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients.

Unique or multiple congenital facial skin polyps are features of several rare syndromes, from the most well-known Pai syndrome (PS), to the less recognized oculoauriculofrontonasal syndrome (OAFNS), encephalocraniocutaneous lipomatosis (ECCL), or Sakoda complex (SC). We set up a research project aiming to identify the molecular bases of PS. We reviewed 27 individuals presenting with a syndromic frontonasal polyp and initially referred for PS. Based on strict clinical classification criteria, we could confirm only nine (33%) typical and two (7%) atypical PS individuals. The remaining ones were either OAFNS (11/27-41%) or presenting with an overlapping syndrome (5/27-19%). Because of the phenotypic overlap between these entities, OAFNS, ECCL, and SC can be either considered as differential diagnosis of PS or part of the same spectrum. Exome and/or genome sequencing from blood DNA in 12 patients and from affected tissue in one patient failed to identify any replication in candidate genes. Taken together, our data suggest that conventional approaches routinely utilized for the identification of molecular etiologies responsible for Mendelian disorders are inconclusive. Future studies on affected tissues and multiomics studies will thus be required in order to address either the contribution of mosaic or noncoding variation in these diseases.

SARCOMA FUSOCELULAR /PLEOMORFICO EN PACIENTE CON SINDROME DE HABERLAND

Introduction: The first case of pediatric spindle cell / pleomorphic sarcoma associated with Haberland syndrome or Encephalocraniocutaneous Lipomatosis, a rare ectomesodermal dysgenesis defined by the triad that includes ocular, skin, and central nervous system involvement, which is usually unilateral, is described. This disorder is attributed to a postzygotic mutation responsible for dysgenesis of the neural tube and crest. Clinical Case: We present the case of a 10-year-old boy, who evolves with developmental delay, motor deficit, intellectual deficit, and epilepsy, associated with spindle cell / pleomorphic sarcoma. We describe his clinical evolution, electroencephalography, and neuroimaging of him. Conclusion: The hypothesis that Haberland syndrome is associated with an increased risk of tumor development is intriguing, although the rarity of the disease currently prevents us from drawing definitive conclusions about this possible link between the two entities. Keywords: Encephalocraniocutaneous lipomatosis, Sarcoma, Epilepsy, Central Nervous System. (Source: MeSH NLM)

Utility of Neonatal Findings in Early Diagnosis of a Case of Haberland Syndrome.

Haberland syndrome or encephalocraniocutaneous lipomatosis (ECCL) is a rare, congenital syndrome characterized by lipomas and noncancerous tumors of the scalp, skin, and eyes, in addition to intellectual disability, early onset seizures, and ectomesodermal dysgenesis. The diagnosis of ECCL is classically made by clinical presentation, imaging, and histopathological findings, but due to the spectrum of clinical presentation and symptom severity, diagnosis is often delayed until adolescence or adulthood. Here we present a newborn male infant, one of the earliest case diagnoses to our knowledge, with a unique constellation of physical exam and neuroimaging findings consistent with this diagnosis. We aim to address important neonatal findings to aid in early detection and diagnosis of this unique disease, which is thought to improve clinical outcomes and patient quality of life.

Ophthalmic Manifestation and Pathological Features in a Cohort of Patients With Linear Nevus Sebaceous Syndrome and Encephalocraniocutaneous Lipomatosis.

Purpose: This study aimed to figure out the association between ophthalmic and pathological features in patients with Linear Nevus Sebaceous Syndrome (LNSS) and in patients with Oculoectodermal Syndrome—Encephalocraniocutaneous Lipomatosis (OES-ECCL).Methods: It is a retrospective, non-consecutive, observational case series. Twenty-seven patients (12 with LNSS and 15 with OES-ECCL, 41 eyes) referred to the Department of Ophthalmology of the Shanghai Ninth People's Hospital between 2000 and 2020 were included. The mean age of the study population for the first-time consult was 5.7 years, ranging from 3 months to 34 years. Clinical notes, pathological records, and imaging findings were reviewed in all the patients.Results: Fourteen (51.9%) cases showed bilateral ocular involvement. Epibulbar choristomas were seen in all the patients. All the lesions involved the conjunctiva and cornea simultaneously. Multiple lesions were observed in 12 eyes. Of the 14 excised lesions, 11 were found to be complex choristomas. Further, 24 (89%) patients had eyelid coloboma. Also, 13 patients (48%) were diagnosed with strabismus, and 12 patients (44%) had abnormal fundus imaging, including optic nerve hypoplasia.Conclusions: LNSS and OES-ECCL shared common ophthalmic features, including epibulbar choristomas with distinctive characteristics, eyelid coloboma, strabismus, and optic nerve hypoplasia. The complex choristoma was found to be associated with the diseases. These specific patterns can be diagnostic clues to distinguish them from other syndromes, such as craniofacial defects, and to remind ophthalmologists that such patients require additional dermatological and neurological examinations and referral. Moreover, a thorough evaluation of ocular conditions is imperative for early interventions.

A rare case of Haberland syndrome

A rare case of Haberland syndrome

Haberland syndrome with bilateral ocular involvement

Haberland syndrome or encephalocutaneous lipomatosis is a very uncommon syndrome that is characterised by changes in the skin, eye, and central nervous system. It was first described in 1970 by Haberland and Perou, with about 60 cases having been reported since then. A case is reported of a 14-week-old male diagnosed with Haberland syndrome with bilateral ocular involvement in the form of palpebral coloboma and choristomas . El síndrome de Haberland o lipomatosis encefalocraneocutánea es un síndrome muy infrecuente caracterizado por la triada clásica de afectación cutánea, ocular y del sistema nervioso central. Fue descrito por primera vez en 1970 por Haberland y Perou, 1 habiéndose reportado unos 60 casos desde entonces. 2 Presentamos un caso de un varón de 14 semanas diagnosticado de síndrome de Haberland con afectación bilateral ocular en forma de coloboma palpebral y coristomas.

RASopathies

RASopathies are a group of disorders characterized by mutations in the RAS-MAPK pathway. RAS-MAP signaling plays a critical role in cell differentiation, proliferation, and survival. Germline mutations can result in distinctive syndromes, including Noonan syndrome, Costello syndrome, and neurofibromatosis type 1. Mosaic RASopathies can present as localized cutaneous lesions like epidermal nevi and nevus sebaceous, or more extensive conditions such as encephalocraniocutaneous lipomatosis. We review the heterogenous presentation of RAS mutations, discuss new targeted therapies, and highlight areas of uncertainty, including carcinogenesis risk and appropriate screening.

Haberland syndrome: Encephalocraniocutaneous syndrome presenting as status epilepticus

Haberland syndrome: Encephalocraniocutaneous syndrome presenting as status epilepticus

Encephalocraniocutaneous lipomatosis with meningioma: A novel presentation of a very rare syndrome

Encephalocraniocutaneous lipomatosis “ECCL” is a rare, sporadic neurocutaneous disorder hypothesized to result from somatic mosaicism caused by lethal autosomal mutations. It is characterized by unilateral involvement of skin, eyes and central nervous system. There are nearly 60 cases reported in the literature. We report a first case of probable ECCL with meningioma. IRB approval was obtained. A 30-year-old male of average IQ presented with recurrent generalized seizures after years of medication-controlled epilepsy. He also displayed multiple left sided skin lesions on the head, torso and limbs, in addition to patches of alopecia and left sided lipomas, prompting evaluation for a possible neurocutaneous syndrome. EEG was unrevealing. Brain CT showed left parietal hypoattenuation with sulcal effacement, left fronto-temporal gyriform calcification, and left relative hemiatrophy. He had history of left mandibular cysts with secondary osteomyelitis. MRI with contrast confirmed the presence of a dural-based enhancing left parasagittal mass. Post-excision cytopathology with immunostaining revealed the mass to be fibrous meningioma, WHO grade I. Ophthalmological evaluation was unremarkable. Whole spine MRI was unrevealing of lipomas. Upon review of literature, the diagnosis of probable encephalocraniocutaneous lipomatosis was made. Sturge-Weber syndrome is a less-likely diagnosis. Biopsy of skin lesions is planned to confirm nevus psiloliparis. The findings of this case reflect the heterogeneity of ECCL as a spectrum of disease. Our first reporting of ECCL with an intracranial neoplasm adds to the scarce literature on this syndrome and lays the ground for future expansion of current criteria.

Expansion of the phenotypic spectrum and description of molecular findings in a cohort of patients with oculocutaneous mosaic RASopathies.

BackgroundPostzygotic KRAS, HRAS, NRAS, and FGFR1 mutations result in a group of mosaic RASopathies characterized by related developmental anomalies in eye, skin, heart, and brain. These oculocutaneous disorders include oculoectodermal syndrome (OES) encephalo‐cranio‐cutaneous lipomatosis (ECCL), and Schimmelpenning‐Feuerstein‐Mims syndrome (SFMS). Here, we report the results of the clinical and molecular characterization of a novel cohort of patients with oculocutaneous mosaic RASopathies.MethodsTwo OES, two ECCL, and two SFMS patients were ascertained in the study. In addition, two subjects with unilateral isolated epibulbar dermoids were also enrolled. Molecular analysis included PCR amplification and Sanger sequencing of KRAS, HRAS, NRAS, and FGFR1 genes in DNA obtained from biopsies (skin/epibulbar dermoids), buccal mucosa, and blood leukocytes. Massive parallel sequencing was employed in two cases with low‐level mosaicism.ResultsIn DNA from biopsies, mosaicism for pathogenic variants, including KRAS p.Ala146Thr in two OES subjects, FGFR1 p.Asn546Lys and KRAS p.Ala146Val in ECCL patients, and KRAS p.Gly12Asp in both SFMS patients, was demonstrated. No mutations were shown in DNA from conjunctival lesions in two subjects with isolated epibubar dermoids.ConclusionOur study allowed the expansion of the clinical spectrum of mosaic RASopathies and supports that mosaicism for recurrent mutations in KRAS and FGFR1 is a commonly involved mechanism in these rare oculocutaneous anomalies.

18F-Fludeoxyglucose Positron-emission Tomography/Computed Tomography in Encephalocraniocutaneous Lipomatosis/Haberland Syndrome.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare disorder and its clinical presentation constitutes a classic triad of the skin, ocular, and central nervous system involvement. We discuss the 18F-fludeoxyglucose positron-emission tomography/computed tomography findings of an 11-year-old boy with ECCL and drug refractory epilepsy.

Anaesthetic management of a case of Haberland's syndrome (encephalocraniocutaneous lipomatosis)

While the Haberland syndrome was first reported in 1970, the anaesthetic management of this rare cohort of patients has not been described. With only 54 such cases reported, describing primarily the unilateral cutaneous, ocular, and neurologic malformations associated with this syndrome without focussing on the anaesthetic management. We describe the case of a 7 year old case of Harberland syndrome with special focus on the difficulties faced by us in mask ventilation, as well as intubation and the need for elective ventilation and planned extubation. We also discuss the precautions to be taken while undertaking such a case like preparations for emergency tracheostomy and possibility of re-intubation after extubation. A meticulous preoperative workup along with neurological and airway examination along with preparation for elective ventilation and tracheostomy is a prerequisite for the successful management of this case.

Up-regulation of fibroblast growth factor receptor 1 due to prenatal tobacco exposure can lead to developmental defects in new born

Introduction: Tobacco-smoking is one of the most important risk factor for preterm delivery, pregnancy loss, low birth weight, and fetal growth restriction. It is estimated that approximately 30% of growth-restricted neonates could be independently associated with maternal smoking.Methods: In this study, gene expression profile, GSE11798, was chosen from GEO database with an aim to perceive change in gene expression signature in new born due to maternal smoking. Enrichment analysis was performed to annotate differentially expressed genes (DEGs) through gene ontology and pathway analysis using DAVID. Protein–protein interactions and module detection of these DEGs were carried out using cytoscape v3.6.0. Thirty umbilical cord tissue samples from 15 smokers and 15 non-smokers pregnant women were included in this analysis.Results: Twenty-six differentially expressed genes (DEGs) between two groups were selected using GEO2R tool. The DEGs were observed to be participating in biological processes/pathways related to growth releasing hormone, angiogenesis, embryonic skeletal, and cardiac development. Fibroblast growth factor receptor-1 (FGFR1) was identified to be the hub node with 348 interacting partners, which regulates transcription, cell growth, differentiation, and apoptosis. The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.Conclusion: The findings manifests the possibility of overcoming these adverse health effects in new born through FGFR1 modulating treatments during pregnancy.

Encephalocraniocutaneous Lipomatosis

A 5-year-old boy presented with worsening headaches for 3 months. On examination, he was found to have a hairless fatty tissue nevus of the scalp (nevus psiloliparus), subcutaneous soft tissue masses on the right side of his face, neck, mandible and right buttock and epibulbar dermoid of the right eye (choristoma) (). Magnetic resonance imaging revealed a large suprasellar mass, which was debulked and found to be a pilocytic astrocytoma. Testing was not performed for the BRAF/KIAA1549 fusion or BRAFV600E mutation. Seven years later, he was started on adjuvant chemotherapy for gradual tumor progression. Over the ensuing 3 years, he had further disease progression despite treatment with 3 frontline chemotherapy regimens: vinblastine, carboplatin/vincristine, and irinotecan/bevacizumab. Targeted sequencing of tissue from the right gluteal mass, revealed a mosaic activating FGFR1 c.1966A>G (p.Lys656Glu) mutation, absent in normal left gluteal tissue, confirming the diagnosis of encephalocraniocutaneous lipomatosis (ECCL), belonging to the family of RASopathies (including neurofibromatosis type I, Noonan syndrome, Costello syndrome), with constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, and an increased risk of developing neoplasms. He was started on trametinib, a MEK inhibitor, off-label, targeting the MAPK pathway downstream from FGFR1, with stable tumor size at last follow-up, after 6 months on therapy.