Superimposed mosaicism in tuberous sclerosis complex: a key to understanding all of the manifold manifestations?
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
21
02
2020
accepted:
10
04
2020
pubmed:
13
5
2020
medline:
15
5
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
In patients with tuberous sclerosis, we can today distinguish between two different categories of segmental mosaicism. The well-known simple segmental mosaicism is characterized by a unilateral or otherwise localized arrangement of the ordinary lesions of the disorder, reflecting heterozygosity for an early postzygotic new mutation. By contrast, superimposed mosaicism is defined by a pronounced segmental involvement in a patient with ordinary non-segmental lesions of the same disorder, resulting in a heterozygous embryo from loss of the corresponding wild-type allele that occurred at a very early developmental stage. So far, the second category has been called 'type 2 segmental mosaicism', but here we propose the short and unambiguous term 'superimposed mosaicism'. In order to render physicians familiar with the manifold manifestations of this category as noted in tuberous sclerosis, we review the following clinical designations under which cases suggesting superimposed mosaicism have been published: forehead plaque; shagreen patch; fibrous cephalic plaque; fibromatous lesion of the scalp; folliculocystic and collagen hamartoma; segmental hypomelanosis; congenital segmental lymphedema; and segmental 'diffuse' lipomatosis. Molecular corroboration of this genetic concept has been provided in a case of forehead plaque and in a child with shagreen patch. - Extracutaneous manifestations suggesting superimposed mosaicism include columnar tuberous brain defects; 'radial migration lines' or 'cerebral white matter migration lines' as noted by brain imaging; linear hamartomatous lesions of the tongue; fibrous dysplasia of bones including macrodactyly; and unilateral overgrowth of an arm or leg. - Remarkably, superimposed mosaicism appears to occur in tuberous sclerosis far more frequently than simple segmental mosaicism.
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2511-2517Informations de copyright
© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
Références
Li S, Takeuchi F, Wang JA et al. Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas. Proc Natl Acad Sci USA 2008; 105: 3539-3544.
Cao J, Tyburczy ME, Moss J et al. Tuberous sclerosis complex inactivation disrupts melanogenesis via mTORC1 activation. J Clin Invest 2017; 127: 349-364.
Crino PB, Aronica E, Baltuch G, Nathanson Kl. Biallelic TSC gene inactivation in tuberous sclerosis complex. Neurology 2010; 74: 1716-1723.
Sampson JR, Harris PC. The molecular genetics of tuberous sclerosis. Hum Mol Genet 1994; 3(suppl_1): 1477-1480.
Henske EP, Wessner LL, Golden J et al. Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol 1997; 151: 1639-1647.
Chan JA, Zhang H, Roberts PS et al. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 2004; 63: 1236-1242.
Bongaarts A, Giannikou K, Reinten RJ et al. Subependymal giant cell astrocytomas in tuberous sclerosis complex have consistent TSC1/TSC2 biallelic inactivation, and no BRAF mutations. Oncotarget 2017; 8: 95516-95529.
Giannikou K, Malinowska IA, Pugh TJ et al. Whole exome sequencing identifies TSC1/TSC2 biallelic loss as the primary and sufficient driver event for renal angiomyolipoma development. PLoS Genet 2016; 12: e1006242.
Happle R. The categories of cutaneous mosaicism: a proposed classification. J Med Genet A 2016; 170A: 452-459.
Mashhood AA, Amjad M. Unilateral tuberous sclerosis complex. J Coll Physicians Surg Pak 2004; 14: 628-630.
Treichel AM, Hamieh L, Nathan NR et al. Phenotypic distinctions between mosaic forms of tuberous sclerosis complex. Genet Med 2019; 21: 2594-2604.
Happle R. A rule concerning the segmental manifestation of autosomal dominant skin disorders. Review of clinical examples providing evidence for dichotomous types of severity. Arch Dermatol 1997; 133: 1505-1509.
Camprubí M, Balaguer A, Azon Masoliver A et al. Unilateral facial angiofibromas; a review of the literature. Pediatr Dermatol 2006; 23: 303-305.
Bordel-Gómez MT, Monteagudo-Sánchez B, Alvarez-Fernández JC. Angiofibromas faciales múltiples unilaterales: aportación de un nuevo caso [Multiple unilateral facial angiofibromas: description of a new case]. Actas Dermosifiliogr 2008; 99: 824-827. [Article in Spanish].
Mittal A, Vinay K, De D et al. Tuberous sclerosis complex and diffuse lipomatosis: case report of a rare association. Indian Dermatol Online J 2018; 9: 37-39.
Granata A, Mignami R. Nephrology image. Shagreen patch. Kidney Int 2009; 75: 1364.
Webb DW, Clarke A, Fryer A, Osborne JP. The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol 1996; 135: 1-5.
Cammarata-Scalisi F, Vidales Moreno C, Stock F et al. Two novel mutations in the TSC2 gene causing severe phenotype in nervous system and skin in a patient with tuberous sclerosis complex. J Eur Acad Dermatol Venereol 2018; 32: e243-e245.
Fryer AE, Osborne JP, Schutt W. Forehead plaque: a presenting skin sign in tuberous sclerosis. Arch Dis Child 1987; 62: 92-293.
Teng JM, Cowen EW, Wataya-Kaneda M et al. Dermatologic and dental aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements. JAMA Dermatol 2014; 150: 1095-1001.
Nguyen Q-BD, DarConte MD, Hebert AA. The cutaneous manifestations of tuberous sclerosis complex. Am J Med Genet Part C 2018; 178C: 321-325.
Oyerinde O, Buccine D, Treichel A et al. Fibrous cephalic plaques in tuberous sclerosis complex. J Am Acad Dermatol 2018; 78: 717-724.
Giacaman A, Martín-Santiago A. Fibrous cephalic plaque in tuberous sclerosis complex: treatment with 0.2% rapamycin. Actas Dermosifiliogr 2019; 110: e13.
Wu Q, Chen H, Elston DM. A firm plaque on the occipital scalp. JAMA Dermatol 2019; 155: 1071.
Baykal C, Tekturk P, Polat Ekinci A et al. Fibromatous lesion of the scalp: is it an underestimated sign of tuberous sclerosis? J Eur Acad Dermatol Venereol 2017; 31: e110-e112.
Torrelo A, Hadj-Rabia S, Colmenero I et al. Folliculocystic and collagen hamartoma of tuberous sclerosis complex. J Am Acad Dermatol 2012; 66: 617-621.
Happle R. Pourquoi les génodermoses autosomiques dominantes ont-elles deux expressions segmentaires différentes? [Why do autosomal dominant genodermatoses have two different segmentary expressions?]. Ann Dermatol Venereol 2001; 128: 109-110. [French].
Reolid A, Navarro R, Daudén E et al. Facial folliculocystic and collagen hamartoma: a variant of fibrous cephalic plaque with prominent cyst formation? J Dtsch Dermatol Ges 2019; 17: 738-741.
An JM, Kim YS, Park YL, Lee S. Folliculocystic and collagen hamartoma: a new entity? Ann Dermatol 2015; 27: 593-596.
Brown MM, Walsh EJ, Yu L, Smidt AC. Progressive scalp plaque in a girl with tuberous sclerosis. Pediatr Dermatol 2014; 31: 249-250.
Kaplan L, Kazlouskaya V, Ugorji R et al. Folliculocystic and collagen hamartoma of tuberous sclerosis: a new case in a female patient and review of literature. J Cutan Pathol 2018; 45: 67-70.
Han HJ, Lim GY, You CY. A large infiltrating fibrous hamartoma of infancy in the abdominal wall with rare associated tuberous sclerosis. Pediatr Radiol 2009; 39: 743-746.
Ortonne JP, Bahadoran P, Fitzpatrick TB et al. Hypomelanoses and hypermelanoses. In Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI eds. Fitzpatrick's Dermatology in General Medicine, 6th edn, McGraw-Hill, New York, 2003: 836-881.
Jindal R, Jain A, Gupta A, Shirazi N. Ash-leaf spots or naevus depigmentosus: a diagnostic challenge. BMJ Case Rep 2013; 2013. https://doi.org/10.1136/bcr-2012-007008
Selvaraj R, Kasturi N, Kumari P, Muraleedharan S. Unilateral cataract associated with eyelid ash-leaf macule in tuberous sclerosis complex. BMJ Case Rep 2018; 2018. https://doi.org/10.1136/bcr-2018-224923
Malissen N, Vergely L, Simon M et al. Long-term treatment of cutaneous manifestations of tuberous sclerosis complex with topical 1% sirolimus cream: a prospective study of 25 patients. J Am Acad Dermatol 2017; 77: 464-472.
Hirsch RJ, Silverberg NB, Laude T, Weinberg JM. Tuberous sclerosis associated with congenital lymphedema. Pediatr Dermatol 1999; 16: 407-408.
Voudris KA, Skardoutsou A, Vagiakou EA. Tuberous sclerosis and congenital lymphedema. Pediatr Dermatol 2003; 20: 371-373.
Sukulal K, Namboodiri N. Congenital lymphedema: another unique and gender specific stigmata of tuberous sclerosis? Indian Pediatr 2012; 49: 845.
Navarre P, Poitras B. Lymphoedema in tuberous sclerosis: case report and review of the literature. J Pediatr Orthop 2014; 34: e27-e32.
Wiemer-Kruel A, Mayer H, Ewert P et al. Congenital lymphatic malformation and aortic aneurysm in a patient with TSC2 mutation. Neuropediatrics 2020; 51: 57-61.
Kaneshi Y, Shibasaki J, Aida N et al. Indocyanine green lymphography for congenital lymphatic dysplasia with tuberous sclerosis complex: a case report. Pediatr Int 2020; 62: 234-236.
Prato G, Mancardi MM, Baglietto MG et al. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with mammalian target of rapamycin inhibitors. J Child Neurol 2014; 29: NP54-NP57.
Hoshiai S, Oguma E, Sato Y et al. Congenital focal lymphedema as a diagnostic clue to tuberous sclerosis complex: report of two cases diagnosed by ultrasound. Skeletal Radiol 2015; 44: 1165-1168.
Alcázar JD, Ramos R, Verdugo J. [Dorsal transthoracic diffuse lipomatosis in a patient with familial tuberous sclerosis]. Arch Bronconeumol 1998; 34: 468-469. [Article in Spanish].
Klein JA, Barr RJ. Diffuse lipomatosis and tuberous sclerosis. Arch Dermatol 1986; 122: 1298-1302.
Happle R. The concept of type 2 segmental mosaicism, expanding from dermatology to general medicine. J Eur Acad Dermatol Venereol 2018; 32: 1075-1088.
Rovira À, Ruiz-Falcó ML, García-Esparza E et al. Recommendations for the radiological diagnosis and follow-up of neuropathological abnormalities associated with tuberous sclerosis complex. J Neurooncol 2014; 118: 205-223.
Griffiths PD, Bolton B, Verity C. White matter abnormalities in tuberous sclerosis complex. Acta Radiol 1998; 39: 482-486.
van Eeghen AM, Terán LO, Johnson J et al. The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines. Neuroradiology 2013; 55: 1007-1014.
Overwater IE, Swenker R, van der Ende EL et al. Genotype and brain pathology phenotype in children with tuberous sclerosis complex. Eur J Hum Genet 2016; 24: 1688-1695.
Amin S, O'Callaghan FJ. Glossal hamartoma in tuberous sclerosis. Arch Dis Child 2013; 98: 161.
Itin PH, Buechner SA. Segmental forms of autosomal dominant skin disorders: the puzzle of mosaicism. Am J Med Genet 1999; 85: 351-354.
Wallace H, Davis A, Spedding A. Tongue-base hamartoma in tuberous sclerosis. J Laryngol Otol 2001; 115: 149-150.
Gross-Tsur V, Klar A, Gazit D, Shalev RS. Unique congenital features in tuberous sclerosis. Clin Pediatr (Phila) 1992; 31: 364-365.
Li P, Boronat S, Geffrey AL et al. Rib and vertebral bone fibrous dysplasia in a child with tuberous sclerosis complex. Am J Med Genet A 2015; 167A: 2755-2757.
Tung HE, Shih SL. Tuberous sclerosis with rare presentation of macrodactyly. Pediatr Radiol 2009; 39: 878.
Ortonne JP, Jeune R, Fulton R, Thivolet J. Primary localized gigantism and tuberous sclerosis. Arch Dermatol 1982; 118: 877-878.
Taneja R, Singh DV. Giant renal angiomyolipoma: unusual cause of huge abdominal mass. J Clin Imaging Sci 2013; 3: 56.
Sohlberg E, Sun A, Massoudi R et al. Giant renal angiomyolipoma in a solitary kidney. Can J Urol 2018; 25: 9614-9616.
Fragkoulis C, Stasinopoulos K, Theocharis G et al. A rare case of giant renal angiomyolipoma in a woman with tuberous sclerosis. Urol Case Rep 2018; 20: 41-42.
Tidim G, Kilickesmez O, Culha MG. Recurrent, giant renal angiomyolipoma treated with selective arterial embolization: a case report. Urol Int 2019; 102: 364-366.
Wang L, Ni D, Zhong L, Wang J. Familial genetic tuberous sclerosis complex associated with bilateral giant renal angiomyolipoma: a case report. Oncol Lett 2017; 14: 7099-7106.
Carter D, Papps B, Brook NR. Disseminated intravascular coagulation after embolization to treat acutely bleeding bilateral massive angiomyolipoma: a case report. J Endourol Case Rep 2018; 4: 117-119.
Tyburczy ME, Wang JA, Li S et al. Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex. Hum Mol Genet 2014; 23: 2023-2029.
García Muret MP, Pujol RM, de Moragas JM. [Multiple and unilateral angiofibromas of the face: forme fruste of Bourneville tuberous sclerosis]. Ann Dermatol Venereol 1998; 125: 325-327. [French].
Garcia-Muret M, Pujol R. [Multiple unilateral angiofibromas of the face]. Ann Dermatol Venereol 2000; 127: 211. [French].
Wendt JR, Watson LR. Cosmetic treatment of shagreen patches in selected patients with tuberous sclerosis. Plast Reconstr Surg 1991; 87: 780-782.
Happle R. Mosaicism in Human Skin: Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia, Springer, Berlin, 2014: 16-18.