Journal of Pediatric Neurology 2020; 18(05): 258-262
DOI: 10.1055/s-0039-1692985
Case Report
Georg Thieme Verlag KG Stuttgart · New York

FGFR1 Mosaic Pathogenic Variant in Encephalocraniocutaneous Lipomatosis with Leptomeningeal Angiomatosis

1   Pediatric Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain
,
Paula Fernández-Álvarez
2   Clinical and Molecular Genetics Department, Vall d'Hebron University Hospital and Medicine Genetics Group VHIR, Barcelona, Spain
,
Ángel Sánchez-Montañez García-Carpintero
3   Neuroradiology Department, Vall d'Hebron University Hospital, Barcelona, Spain
,
Vicenç García-Patos&
4   Pediatric Dermatology Department, Vall d'Hebron University Hospital, Barcelona, Spain
,
Eduardo F. Tizzano&
2   Clinical and Molecular Genetics Department, Vall d'Hebron University Hospital and Medicine Genetics Group VHIR, Barcelona, Spain
,
Susana Boronat*&
1   Pediatric Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain
2   Clinical and Molecular Genetics Department, Vall d'Hebron University Hospital and Medicine Genetics Group VHIR, Barcelona, Spain
› Author Affiliations
Further Information

Publication History

04 April 2019

27 May 2019

Publication Date:
01 July 2019 (online)

Abstract

Encephalocraniocutaneous lipomatosis (ECCL) is a congenital neurocutaneous disorder. It is characterized by ocular anomalies (epibulbar choristomas), skin lesions (as nevus psiloliparus and subcutaneous lipomas), and central nervous system abnormalities (mostly arachnoid cysts, brain anomalies, vascular defects, and intracranial and spinal lipomas). Mutations in KRAS and fibroblast growth factor receptor gene-1 (FGFR1) are related to ECCL, explaining additional manifestations such as jaw tumors or gliomas. We report a pediatric patient with clinical, radiological, and histological findings consistent with ECCL and a mosaic pathogenic variant in FGFR1 found in the DNA from a non-cultured biopsy of the nevus psiloliparus and absent in blood and DNA from buccal mucosa.

* Authors' present address:


Marta Gómez-García de la Banda: Pediatric Neurology Department, Neuromuscular Disorders Unit. Raymond-Poincaré University Hospital, APHP CHU Paris IdF Ouest, Garches (France).


Susana Boronat: Pediatric Neurology Department, Sagrat Cor University Hospital, Barcelona (Spain).


& Senior authors


 
  • References

  • 1 Sofiatti A, Cirto AG, Arnone M. , et al. Encephalocraniocutaneous lipomatosis: clinical spectrum of systemic involvement. Pediatr Dermatol 2006; 23 (01) 27-30
  • 2 Ardinger HH, Horii KA, Begleiter ML. Expanding the phenotype of oculoectodermal syndrome: possible relationship to encephalocraniocutaneous lipomatosis. Am J Med Genet A 2007; 143A (24) 2959-2962
  • 3 Moog U, Jones MC, Viskochil DH, Verloes A, Van Allen MI, Dobyns WB. Brain anomalies in encephalocraniocutaneous lipomatosis. Am J Med Genet A 2007; 143A (24) 2963-2972
  • 4 Moog U. Encephalocraniocutaneous lipomatosis. J Med Genet 2009; 46 (11) 721-729
  • 5 Peacock JD, Dykema KJ, Toriello HV. , et al. Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations. Am J Med Genet A 2015; 167 (07) 1429-1435
  • 6 Boppudi S, Bögershausen N, Hove HB. , et al. Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. Clin Genet 2016; 90 (04) 334-342
  • 7 Bennett JT, Tan TY, Alcantara D. , et al; University of Washington Center for Mendelian Genomics; Care4Rare Canada Consortium. Mosaic activating mutations in FGFR1 cause encephalocraniocutaneous lipomatosis. Am J Hum Genet 2016; 98 (03) 579-587
  • 8 Phi JH, Park SH, Chae JH, Wang KC, Cho BK, Kim SK. Papillary glioneuronal tumor present in a patient with encephalocraniocutaneous lipomatosis: case report. Neurosurgery 2010; 67 (04) E1165-E1169
  • 9 Valera ET, Brassesco MS, Scrideli CA. , et al. Are patients with encephalocraniocutaneous lipomatosis at increased risk of developing low-grade gliomas?. Childs Nerv Syst 2012; 28 (01) 19-22
  • 10 Bieser S, Reis M, Guzman M. , et al. Grade II pilocytic astrocytoma in a 3-month-old patient with encephalocraniocutaneous lipomatosis (ECCL): case report and literature review of low grade gliomas in ECCL. Am J Med Genet A 2015; 167A (04) 878-881
  • 11 Kocak O, Yarar C, Carman KB. Encephalocraniocutaneous lipomatosis, a rare neurocutaneous disorder: report of additional three cases. Childs Nerv Syst 2016; 32 (03) 559-562
  • 12 Haberland C, Perou M. Encephalocraniocutaneous lipomatosis. A new example of ectomesodermal dysgenesis. Arch Neurol 1970; 22 (02) 144-155
  • 13 López Sousa M, Varela Iglesias J, Bouzón Alejandro M, Lojo Rodríguez M, Pérez Muñuzuri A, Fernández Lorenzo JR. Encephalocraniocutaneous lipomatosis (Haberland syndrome) with bilateral ocular damage [in Spanish]. An Pediatr (Barc) 2007; 66 (06) 619-621
  • 14 Valladares MJ, Blanco MJ, Lopez-Lopez F, Gonzalez F. Bilateral ocular involvement in encephalocraniocutaneous lipomatosis. Eur J Paediatr Neurol 2007; 11 (02) 108-110
  • 15 Radić Nišević J, Prpić I, Antulov R, Sasso A, Holjar Erlić I. Encephalocraniocutaneous lipomatosis without ocular malformations. Pediatr Neurol 2016; 60: 71-74
  • 16 Valera ET, McConechy MK, Gayden T. , et al. Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas. Acta Neuropathol 2018; 136 (04) 657-660
  • 17 Shirley MD, Tang H, Gallione CJ. , et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013; 368 (21) 1971-1979
  • 18 Jordan PR, Iqbal M, Prasad M. Sturge-Weber syndrome type 3 manifesting as ‘Status migrainosus.’. BMJ Case Rep 2016 2016. :pii: bcr2016216842
  • 19 Brassesco MS, Valera ET, Becker AP. , et al. Low-grade astrocytoma in a child with encephalocraniocutaneous lipomatosis. J Neurooncol 2010; 96 (03) 437-441
  • 20 Fukaya R, Ozaki M, Kamamoto D. , et al. Significant antitumor response of disseminated glioblastoma to bevacizumab resulting in long-term clinical remission in a patient with encephalocraniocutaneous lipomatosis: A case report. Mol Clin Oncol 2016; 5 (04) 417-421
  • 21 Han JY, Yum MS, Kim EH, Hong S, Ko TS. A rare case of dysembryoplastic neuroepithelial tumor combined with encephalocraniocutaneous lipomatosis and intractable seizures. Korean J Pediatr 2016; 59 (Suppl. 01) S139-S144