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Genodermatoses associated with melanocytic nevi

      Abstract

      Though melanocytic nevi are ubiquitous in the general population, they can also be key cutaneous manifestations of genetic syndromes. We describe genodermatoses associated with melanocytic nevi and discuss their clinical characteristics, cutaneous manifestations, underlying genetics, and, if applicable, guidelines for when genetic testing should be performed. We categorized these genodermatoses based on their association with congenital nevi, acquired nevi, or nevi whose first appearance is unknown. In many cases, the distinctive morphology or distribution of melanocytic nevi can be an important clue that an underlying genetic syndrome is present, allowing both the patient as well as family members to be screened for the more serious complications of their genetic disorder and receive education on potential preventative measures. As we continue to advance our understanding of how various genotypes give rise to the wide spectrum of phenotypes observed in these genodermatoses, we shall be able to better stratify risk and tailor our screening methods to clinically manage the heterogeneous manifestations of genodermatoses among these patients.
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      References

        • Schaffer JV.
        Update on melanocytic nevi in children.
        Clin Dermatol. 2015; 33: 368-386
        • Marghoob AA
        • Orlow SJ
        • Kopf AW.
        Syndromes associated with melanocytic nevi.
        J Am Acad Dermatol. 1993; 29: 373-388
        • Soyer PH
        • Argenziano G
        • Hofmann-Wellenhof R
        • Johr RH
        Color Atlas of Melanocytic Lesions of the Skin.
        Springer, Berlin, Germany2007: 1-351
        • Correa R
        • Salpea P
        • Stratakis CA.
        Carney complex: an update.
        Eur J Endocrinol. 2015; 173: M85-M97
        • Andrici J
        • Gill AJ
        • Hornick JL.
        Next generation immunohistochemistry: emerging substitutes to genetic testing?.
        Semin Diagn Pathol. 2018; 35: 161-169
        • Stratakis CA
        • Kirschner LS
        • Carney JA.
        Clinical and molecular features of the Carney complex: patient evaluation.
        J Clin Endocrinol Metab. 2001; 86: 4041-4046
        • Mateus C
        • Palangié A
        • Franck N
        • et al.
        Heterogeneity of skin manifestations in patients with Carney complex.
        J Am Acad Dermatol. 2008; 59: 801-810
        • Leventhal JS
        • Braverman IM.
        Skin manifestations of endocrine and neuroendocrine tumors.
        Semin Oncol. 2016; 43: 335-340
        • Horvath A
        • Stratakis CA.
        Carney complex and lentiginosis.
        Pigment Cell Melanoma Res. 2009; 22: 580-587
        • Salpea P
        • Horvath A
        • London E
        • et al.
        Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing.
        J Clin Endocrinol Metab. 2014; 99: E183-E188
        • Guggisberg D
        • Hadj-Rabia S
        • Viney C
        • et al.
        Skin markers of occult spinal dysraphism in children: a review of 54 cases.
        Arch Dermatol. 2004; 140: 1109-1115
        • Pires CR
        • de Medeiros JMM
        • Araujo Júnior E
        • Czapkowski A
        • Zanforlin Filho SM
        Occult spinal dysraphism in the presence of rare cutaneous stigma in a neonate: importance of ultrasound and magnetic resonance imaging.
        Case Rep Med. 2013; 2013468376
        • Kumar Sarin Y
        Cutaneous stigmata of occult spinal dysraphism.
        J Neonatal Surg. 2013; 2: 15
        • O'Neill BR
        • Gallegos D
        • Herron A
        • et al.
        Use of magnetic resonance imaging to detect occult spinal dysraphism in infants.
        J Neurosurg Pediatr. 2017; 19: 217-226
        • Proctor MR
        • Bauer SB
        • Scott RM.
        The effect of surgery for split spinal cord malformation on neurologic and urologic function.
        Pediatr Neurosurg. 2000; 32: 13-19
        • Netto JM
        • Bastos AN
        • Figueiredo AA
        • Pérez LM.
        Spinal dysraphism: a neurosurgical review for the urologist.
        Rev Urol. 2009; 11: 71-81
        • O'Neill BR
        • Gallegos D
        • Herron A
        • et al.
        Use of magnetic resonance imaging to detect occult spinal dysraphism in infants.
        J Neurosurg. 2017; 19: 217-226
        • Scottoni F
        • Iacobelli BD
        • Zaccara AM
        • Totonelli G
        • Schingo AMS
        • Bagolan P.
        Spinal ultrasound in patients with anorectal malformations: is this the end of an era?.
        Pediatr Surg Int. 2014; 30: 829-831
        • Wilson P
        • Hayes E
        • Barber A
        • Lohr J.
        Screening for spinal dysraphisms in newborns with sacral dimples.
        Clin Pediatr (Phila). 2016; 55: 1064-1070
        • Chern JJ
        • Aksut B
        • Kirkman JL
        • et al.
        The accuracy of abnormal lumbar sonography findings in detecting occult spinal dysraphism: a comparison with magnetic resonance imaging.
        J Neurosurg Pediatr. 2012; 10: 150-153
        • Cohen MM.
        Let's call it  “Crouzonodermoskeletal syndrome” so we won't be prisoners of our own conventional terminology.
        Am J Med Genet. 1999; 84 (74-74)
        • Meyers GA
        • Orlow SJ
        • Munro IR
        • Przylepa KA
        • Jabs EW.
        Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.
        Nat Genet. 1995; 11: 462-464
        • Ginés E
        • Rodriguez-Pichardo A
        • Jorquera E
        • Moreno JC
        • Camacho F.
        Crouzon disease with acanthosis nigricans and melanocytic nevi.
        Pediatr Dermatol. 1996; 13: 18-21
        • Mir A
        • Wu T
        • Orlow SJ.
        Cutaneous features of Crouzon syndrome with acanthosis nigricans.
        JAMA Dermatology. 2013; 149: 737-741
        • Arnaud-López L
        • Fragoso J
        • Mantilla-Capacho J
        • Barros-Núñez P.
        Crouzon with acanthosis nigricans. Further delineation of the syndrome.
        Clin Genet. 2007; 72: 405-410
        • Kinsler VA
        • Thomas AC
        • Ishida M
        • et al.
        Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.
        J Invest Dermatol. 2013; 133: 2229-2236
        • Lovett A
        • Maari C
        • Decarie JC
        • et al.
        Large congenital melanocytic nevi and neurocutaneous melanocytosis: one pediatric center's experience.
        J Am Acad Dermatol. 2009; 61: 766-774
        • Kadonaga JN
        • Frieden IJ.
        Neurocutaneous melanosis: definition and review of the literature.
        J Am Acad Dermatol. 1991; 24: 747-755
        • Shah KN.
        The risk of melanoma and neurocutaneous melanosis associated with congenital melanocytic nevi.
        Semin Cutan Med Surg. 2010; 29: 159-164
        • Marghoob AA
        • Dusza S
        • Oliveria S
        • Halpern AC.
        Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi.
        Arch Dermatol. 2004; 140: 171-175
        • Kinsler VA
        • Chong WK
        • Aylett SE
        • Atherton DJ.
        Complications of congenital melanocytic naevi in children: analysis of 16 years’ experience and clinical practice.
        Br J Dermatol. 2008; 159: 907-914
        • Jakchairoongruang K
        • Khakoo Y
        • Beckwith M
        • Barkovich AJ.
        New insights into neurocutaneous melanosis.
        Pediatr Radiol. 2018; 48: 1786-1796
        • DeDavid M
        • Orlow SJ
        • Provost N
        • et al.
        Neurocutaneous melanosis: clinical features of large congenital melanocytic nevi in patients with manifest central nervous system melanosis.
        J Am Acad Dermatol. 1996; 35: 529-538
        • Hale EK
        • Stein J
        • Ben-Porat L
        • et al.
        Association of melanoma and neurocutaneous melanocytosis with large congenital melanocytic naevi—results from the NYU-LCMN registry.
        Br J Dermatol. 2005; 152: 512-517
        • Balin SJ
        • Barnhill RL
        Benign melanocytic neoplasms. 4th ed. Philadelphia: Elsevier, 2018: 1954-1988
        • Ramaswamy V
        • Delaney H
        • Haque S
        • Marghoob A
        • Khakoo Y.
        Spectrum of central nervous system abnormalities in neurocutaneous melanocytosis.
        Dev Med Child Neurol. 2012; 54: 563-568
        • Foster RD
        • Williams ML
        • Barkovich AJ
        • Hoffman WY
        • Mathes SJ
        • Frieden IJ.
        Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.
        Plast Reconstr Surg. 2001; 107: 933-941
        • Antonov NK
        • Ruzal-Shapiro CB
        • Morel KD
        • et al.
        Feed and wrap MRI technique in infants.
        Clin Pediatr (Phila). 2017; 56: 1095-1103
        • Sarnat HB
        • Flores-Sarnat L.
        Genetics of neural crest and neurocutaneous syndromes.
        Handb Clin Neurol. 2013; 111: 309-314
        • Lihua J
        • Feng G
        • Shanshan M
        • Jialu X
        • Kewen J.
        Somatic KRAS mutation in an infant with linear nevus sebaceous syndrome associated with lymphatic malformations.
        Medicine (Baltimore). 2017; 96: e8016
        • Flores-Sarnat L
        • Sarnat HB.
        Phenotype/genotype correlations in epidermal nevus syndrome as a neurocristopathy.
        Handb Clin Neurol. 2015; 132: 9-25
        • Rogers M
        • McCrossin I
        • Commens C.
        Epidermal nevi and the epidermal nevus syndrome.
        J Am Acad Dermatol. 1989; 20: 476-488
        • Sun BK
        • Saggini A
        • Sarin KY
        • et al.
        Mosaic activating RAS mutations in nevus sebaceus and nevus sebaceus syndrome.
        J Invest Dermatol. 2013; 133: 824-827
        • Paller AS
        • Syder AJ
        • Chan YM
        • et al.
        Genetic and clinical mosaicism in a type of epidermal nevus.
        N Engl J Med. 1994; 331: 1408-1415
        • Levinsohn JL
        • Tian LC
        • Boyden LM
        • et al.
        Whole-exome sequencing reveals somatic mutations in HRAS and KRAS, which cause nevus sebaceus.
        J Invest Dermatol. 2013; 133: 827-830
        • Idriss MH
        • Elston DM.
        Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases.
        J Am Acad Dermatol. 2014; 70: 332-337
        • Aslam A
        • Salam A
        • Griffiths CEM
        • Mcgrath JA.
        Naevus sebaceus: a mosaic RASopathy.
        Clin Exp Dermatol. 2014; 39: 1-6
        • Eisen DB
        • Michael DJ.
        Sebaceous lesions and their associated syndromes: part II.
        J Am Acad Dermatol. 2009; 61: 563-580
        • Kuroda Y
        • Ohashi I
        • Enomoto Y
        • et al.
        A postzygotic NRAS mutation in a patient with Schimmelpenning syndrome.
        Am J Med Genet Part A. 2015; 167A: 2223-2225
        • Rijntjes-Jacobs EGJ
        • Lopriore E
        • Steggerda SJ
        • Kant SG
        • Walther FJ.
        Discordance for Schimmelpenning-Feuerstein-Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation.
        Am J Med Genet A. 2010; 152A: 2816-2819
        • Kamyab-Hesari K
        • Seirafi H
        • Jahan S
        • et al.
        Nevus sebaceus: a clinicopathological study of 168 cases and review of the literature.
        Int J Dermatol. 2016; 55: 193-200
        • Carlson JA
        • Cribier B
        • Nuovo G
        • Rohwedder A.
        Epidermodysplasia verruciformis-associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn.
        J Am Acad Dermatol. 2008; 59: 279-294
        • Kim D
        • Benjamin LT
        • Sahoo MK
        • Kim J
        • Pinsky BA.
        Human papilloma virus is not prevalent in nevus sebaceus.
        Pediatr Dermatol. 2014; 31: 326-330
        • Happle R.
        Phacomatosis pigmentovascularis revisited and reclassified.
        Arch Dermatol. 2005; 141: 385-388
        • Fernández-Guarino M
        • Boixeda P
        • de las Heras E
        • Aboin S
        • García-Millán C
        • Olasolo PJ.
        Phakomatosis pigmentovascularis: clinical findings in 15 patients and review of the literature.
        J Am Acad Dermatol. 2008; 58: 88-93
        • Baselga E.
        Vascular malformations.
        in: Bolognia JL Schaffer JV Cerroni L Dermatology. 4th ed. Elsevier, Philadelphia2018: 1805-1827
        • Thomas AC
        • Zeng Z
        • Rivière JB
        • et al.
        Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis.
        J Invest Dermatol. 2016; 136: 770-778
      1. Mize DE, Bishop M, Resse E, Sluzevich J. Familial atypical multiple mole melanoma syndrome. Available at: https://www.ncbi.nlm.nih.gov/books/NBK7030/pdf/Bookshelf_NBK7030.pdf. Accessed December 12, 2018.

        • Soura E
        • Eliades PJ
        • Shannon K
        • Stratigos AJ
        • Tsao H.
        Hereditary melanoma: update on syndromes and management: genetics of familial atypical multiple mole melanoma syndrome.
        J Am Acad Dermatol. 2016; 74: 395-410
        • Plaza JA
        • Prieto VG.
        Pathology of Pigmented Skin Lesions.
        Springer Berlin Heidelberg, Berlin, Germany2017
        • Leachman SA
        • Lucero OM
        • Sampson JE
        • et al.
        Identification, genetic testing, and management of hereditary melanoma.
        Cancer Metastasis Rev. 2017; 36: 77-90
        • Gruis NA
        • van der Velden PA
        • Sandkuijl LA
        • et al.
        Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds.
        Nat Genet. 1995; 10: 351-353
        • Hussussian CJ
        • Struewing JP
        • Goldstein AM
        • et al.
        Germline p16 mutations in familial melanoma.
        Nat Genet. 1994; 8: 15-21
        • Marzuka-Alcalá A
        • Gabree MJ
        • Tsao H.
        Melanoma susceptibility genes and risk assessment.
        Methods Mol Biol. 2014; 1102: 381-393
        • Lynch HT
        • Brand RE
        • Hogg D
        • et al.
        Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome.
        Cancer. 2002; 94: 84-96
        • Måsbäck A
        • Olsson H
        • Westerdahl J
        • et al.
        Clinical and histopathological features of malignant melanoma in germline CDKN2A mutation families.
        Melanoma Res. 2002; 12: 549-557
        • Gillgren P
        • Brattströ G
        • Frisell J
        • Palmgren J
        • Ringborg U
        • Hansson J.
        Body site of cutaneous malignant melanoma-a study on patients with hereditary and multiple sporadic tumours.
        Melanoma Res. 2003; 13: 279-286
        • Leachman SA
        • Carucci J
        • Kohlmann W
        • et al.
        Selection criteria for genetic assessment of patients with familial melanoma.
        J Am Acad Dermatol. 2009; 61 (e1-677.e14): 677
        • Jen M
        • Nallasamy S.
        Ocular manifestations of genetic skin disorders.
        Clin Dermatol. 2016; 34: 242-275
        • Fassihi H
        • Sethi M
        • Fawcett H
        • et al.
        Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect.
        Proc Natl Acad Sci U S A. 2016; 113: E1236-E1245
        • Bradford PT
        • Goldstein AM
        • Tamura D
        • et al.
        Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.
        J Med Genet. 2011; 48: 168-176
        • Brooks BP
        • Thompson AH
        • Bishop RJ
        • et al.
        Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage.
        Ophthalmology. 2013; 120: 1324-1336
        • Anttinen A
        • Koulu L
        • Nikoskelainen E
        • et al.
        Neurological symptoms and natural course of xeroderma pigmentosum.
        Brain. 2008; 131: 1979-1989
        • Inoue Y
        • Yamaizumi M
        • nevi Ono T.Group D xeroderma pigmentosum: a case with a number of nevocellular
        J Dermatol. 1995; 22: 360-364
        • Malvehy J
        • Puig S
        • Martí-Laborda RM.
        Dermoscopy of skin lesions in two patients with xeroderma pigmentosum.
        Br J Dermatol. 2005; 152: 271-278
        • Masaki T
        • Wang Y
        • Digiovanna JJ
        • et al.
        High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients.
        Pigment Cell Melanoma Res. 2014; 27: 454-464
        • Haugh AM
        • Njauw C
        • Bubley JA
        • et al.
        Genotypic and Phenotypic Features of BAP1 Cancer Syndrome.
        JAMA Dermatology. 2017; 153: 999-1006
        • Carbone M
        • Yang H
        • Pass HI
        • Krausz T
        • Testa JR
        • Gaudino G
        BAP1 and cancer.
        Nat Rev Cancer. 2013; 13: 153-159
        • Fang Y
        • Fu D
        • Shen XZ.
        The potential role of ubiquitin c-terminal hydrolases in oncogenesis.
        Biochim Biophys Acta. 2010; 1806: 1-6
        • Yélamos O
        • Navarrete-Dechent C
        • Marchetti MA
        • et al.
        Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: results of a multicenter case-control study by the International Dermoscopy Society.
        J Am Acad Dermatol. 2019; 80: 1585-1593
        • Wiesner T
        • Murali R
        • Fried I
        • et al.
        A distinct subset of atypical Spitz tumors is characterized by BRAF mutation and loss of BAP1 expression.
        Am J Surg Pathol. 2012; 36: 818-830
        • King R
        • Googe PB
        • Weilbaecher KN
        • Mihm MC
        • Fisher DE.
        Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors.
        Am J Surg Pathol. 2001; 25: 51-57
        • Garraway LA
        • Widlund HR
        • Rubin MA
        • et al.
        Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.
        Nature. 2005; 436: 117-122
        • Ugurel S
        • Houben R
        • Schrama D
        • et al.
        Microphthalmia-associated transcription factor gene amplification in metastatic melanoma is a prognostic marker for patient survival, but not a predictive marker for chemosensitivity and chemotherapy response.
        Clin Cancer Res. 2007; 13: 6344-6350
        • Nybakken GE
        • Sargen M
        • Abraham R
        • Zhang PJ
        • Ming M
        • Xu X.
        MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.
        Am J Dermatopathol. 2013; 35: 25-29
        • Yokoyama S
        • Woods SL
        • Boyle GM
        • et al.
        A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma.
        Nature. 2011; 480: 99-103
        • Bertolotto C
        • Lesueur F
        • Giuliano S
        • et al.
        A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.
        Nature. 2011; 480: 94-98
        • Leclerc J
        • Ballotti R
        • Bertolotto C.
        Pathways from senescence to melanoma: focus on MITF sumoylation.
        Oncogene. 2017; 36: 6659-6667
        • Sturm RA
        • Fox C
        • McClenahan P
        • et al.
        Phenotypic characterization of nevus and tumor patterns in MITF E318K mutation carrier melanoma patients.
        J Invest Dermatol. 2014; 134: 141-149
        • Potrony M
        • Puig-Butille JA
        • Aguilera P
        • et al.
        Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations.
        JAMA Dermatol. 2016; 152: 405-412
        • Kawakami A
        • Fisher DE.
        The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology.
        Lab Invest. 2017; 97: 649-656
        • Tassabehji M
        • Newton VE
        • Read AP.
        Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene.
        Nat Genet. 1994; 8: 251-255
        • Smith SD
        • Kelley PM
        • Kenyon JB
        • Hoover D.
        Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF.
        J Med Genet. 2000; 37: 446-448
        • Tachibana M.
        MITF: a stream flowing for pigment cells.
        Pigment Cell Res. 2000; 13: 230-240
        • Carvalho AB
        • Lemos-Marini SHV
        • Guerra-Junior G
        • Maciel-Guerra AT.
        Clinical and cytogenetic features of 516 patients with suspected Turner syndrome—a single-center experience.
        J Pediatr Endocrinol Metab. 2018; 31: 167-173
        • Lowenstein EJ
        • Kim KH
        • Glick SA.
        Turner's syndrome in dermatology.
        J Am Acad Dermatol. 2004; 50: 767-776
        • Chodirker BN
        • Harman CR
        • Greenberg CR.
        Spontaneous resolution of a cystic hygroma in a fetus with Turner syndrome.
        Prenat Diagn. 1988; 8: 291-296
        • von Kaisenberg CS
        • Nicolaides KH
        • Brand-Saberi B.
        Lymphatic vessel hypoplasia in fetuses with Turner syndrome.
        Hum Reprod. 1999; 14: 823-826
        • Zvulunov A
        • Wyatt DT
        • Laud PW
        • Esterly NB.
        Influence of genetic and environmental factors on melanocytic naevi: a lesson from Turner's syndrome.
        Br J Dermatol. 1998; 138: 993-997
        • Lemli L
        • Smith DW.
        The XO syndrome: a study of the differentiated phenotype in 25 patients.
        J Pediatr. 1963; 63: 577-588
        • Schoemaker MJ
        • Swerdlow AJ
        • Higgins CD
        • Wright AF
        • Jacobs PA.
        Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study.
        Lancet Oncol. 2008; 9: 239-246
        • Gibbs P
        • Brady BM
        • Gonzalez R
        • Robinson WA.
        Nevi and melanoma: lessons from Turner's syndrome.
        Dermatology. 2001; 202: 1-3
        • Brazzelli V
        • Larizza D
        • Martinetti M
        • et al.
        Halo nevus, rather than vitiligo, is a typical dermatologic finding of turner's syndrome: clinical, genetic, and immunogenetic study in 72 patients.
        J Am Acad Dermatol. 2004; 51: 354-358
        • Spitz JL.
        Disorders with chromosome abnormalities.
        Genodermatoses. 2nd ed. Lippincott Williams & Wilkins, Philadelphia2005: 346-358
        • Roberts AE
        • Allanson JE
        • Tartaglia M
        • Gelb BD
        Noonan syndrome.
        Lancet. 2013; 381: 333-342
        • Zhang J
        • Zhang F
        • Niu R.
        Functions of Shp2 in cancer.
        J Cell Mol Med. 2015; 19: 2075-2083
        • Jongmans MCJ
        • van der Burgt I
        • Hoogerbrugge PM
        • et al.
        Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation.
        Eur J Hum Genet. 2011; 19: 870-874
        • Kratz CP
        • Franke L
        • Peters H
        • et al.
        Cancer spectrum and frequency among children with Noonan, Costello and cardio-facio-cutaneous syndromes.
        Br J Cancer. 2015; 112: 1392-1397
        • Ijiri R
        • Tanaka Y
        • Keisuke K
        • Masuno M
        • Imaizumi K.
        A case of Noonan's syndrome with possible associated neuroblastoma.
        Pediatr Radiol. 2000; 30: 432-433
        • Lopez-Miranda B
        • Westra SJ
        • Yazdani S
        • Boechat MI.
        Noonan syndrome associated with neuroblastoma: a case report.
        Pediatr Radiol. 1997; 27: 324-326
        • Jongmans MC
        • Hoogerbrugge PM
        • Hilkens L
        • et al.
        Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma.
        Genes, Chromosom Cancer. 2010; 49: 635-641
        • Villani A
        • Greer MC
        • Kalish JM
        • et al.
        Recommendations for cancer surveillance in individuals with RASopathies and other rare genetic conditions with increased cancer risk.
        Clin Cancer Res. 2017; 23: e83-e90
        • Bessis D
        • Morice-Picard F
        • Bourrat E
        • et al.
        Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.
        Br J Dermatol. 2019; 180: 172-180
        • Tchanque-Fossuo CN
        • Dahle SE
        • Kiuru M
        • Isseroff RR.
        Vitiligo and melanocytic nevi: new findings in Coffin-Siris syndrome associated with ARID1 germline mutation.
        JAAD Case Rep. 2019; 5: 50-53
        • Tsurusaki Y
        • Okamoto N
        • Ohashi H
        • et al.
        Coffin-Siris syndrome is a SWI/SNF complex disorder.
        Clin Genet. 2014; 85: 548-554
        • Kosho T
        • Miyake N
        • Carey JC.
        Coffin-Siris syndrome and related disorders involving components of the BAF (mSWI/SNF) complex: historical review and recent advances using next generation sequencing.
        Am J Med Genet Part C Semin Med Genet. 2014; 166C: 241-251
        • Santen GWE
        • Clayton-Smith J
        The ARID1B phenotype: what we have learned so far.
        Am J Med Genet Part C Semin Med Genet. 2014; 166: 276-289
        • Gripp KW
        • Baker L
        • Telegrafi A
        • Monaghan KG.
        The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes.
        Am J Med Genet Part A. 2016; 170: 1754-1762
        • Tsurusaki Y
        • Okamoto N
        • Ohashi H
        • et al.
        Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.
        Nat Genet. 2012; 44: 376-378
        • Shain AH
        • Yeh I
        • Kovalyshyn I
        • et al.
        The genetic evolution of melanoma from precursor lesions.
        N Engl J Med. 2015; 373: 1926-1936
        • Hodis E
        • Watson IR
        • Kryukov GV
        • et al.
        A landscape of driver mutations in melanoma.
        Cell. 2012; 150: 251-263
        • Glorio R
        • Haas R
        • Jaimovich L.
        Ectrodactyly, ectodermal dysplasia and clefting (EEC) syndrome.
        J Eur Acad Dermatol Venereol. 2003; 17: 356-358
        • Celli J
        • Duijf P
        • Hamel BC
        • et al.
        Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome.
        Cell. 1999; 99: 143-153
        • Barrow LL
        • van Bokhoven H
        • Daack-Hirsch S
        • et al.
        Analysis of the p63 gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts.
        J Med Genet. 2002; 39: 559-566
        • Yang A
        • Schweitzer R
        • Sun D
        • et al.
        p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development.
        Nature. 1999; 398: 714-718
        • Mills AA
        • Zheng B
        • Wang XJ
        • Vogel H
        • Roop DR
        • Bradley A.
        p63 is a p53 homologue required for limb and epidermal morphogenesis.
        Nature. 1999; 398: 708-713
        • Hyder Z
        • Beale V
        • O'Connor R
        • Clayton-Smith J
        Genitourinary malformations: an under-recognized feature of ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome.
        Clin Dysmorphol. 2017; 26: 78-82
        • Buss PW
        • Hughes HE
        • Clarke A.
        Twenty-four cases of the EEC syndrome: clinical presentation and management.
        J Med Genet. 1995; 32: 716-723
        • Goeminne L.
        A new probably X-linked inherited syndrome: congenital muscular torticollis, multiple keloids cryptorchidism and renal dysplasia.
        Acta Genet Med Gemellol (Roma). 1968; 17: 439-467
        • Marneros AG
        • Norris JE
        • Olsen BR
        • Reichenberger E.
        Clinical genetics of familial keloids.
        Arch Dermatol. 2001; 137: 1429-1434
        • Zuffardi O
        • Fraccaro M.
        Gene mapping and serendipity. The locus for torticollis, keloids, cryptorchidism and renal dysplasia (31430, McKusick) is at Xq28, distal to the G6PD locus.
        Hum Genet. 1982; 62: 280-281
        • Barnes AM
        • Duncan G
        • Weis M
        • et al.
        Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations.
        Hum Mutat. 2013; 34: 1279-1288
        • Petajan JH
        • Momberger GL
        • Aase J
        • Wright DG.
        Arthrogryposis Syndrome (Kuskokwim disease) in the Eskimo.
        JAMA. 1969; 209: 1481-1486
        • Itin PH.
        Etiology and pathogenesis of ectodermal dysplasias.
        Am J Med Genet A. 2014; 164A: 2472-2477
        • Kantaputra P
        • Kaewgahya M
        • Jotikasthira D
        • Kantaputra W.
        Tricho-odonto-onycho-dermal dysplasia and WNT10A mutations.
        Am J Med Genet A. 2014; 164A: 1041-1048
        • Pinheiro M
        • Freire-Maia N
        • Roth AJ
        • Opitz JM.
        Trichoodontoonychial dysplasia—a new meso-ectodermal dysplasia.
        Am J Med Genet. 1983; 15: 67-70
        • Baraitser M
        • Insley J
        • Winter RM.
        A recognisable short stature syndrome with premature aging and pigmented naevi.
        J Med Genet. 1988; 25: 53-56
        • Passarelli PC
        • Pasquantonio G
        • Manicone PF
        • et al.
        Orofacial signs and dental abnormalities in patients with Mulvihill-Smith syndrome.
        Medicine (Baltimore). 2018; 97: e0656
        • Yagihashi T
        • Kato M
        • Izumi K
        • et al.
        Case report: adult phenotype of Mulvihill-Smith syndrome.
        Am J Med Genet Part A. 2009; 149A: 496-500
        • Breinis P
        • Alves FG
        • Alves CA
        • et al.
        The eleventh reported case of Mulvihill-Smith syndrome in the literature.
        BMC Neurol. 2014; 14: 4
        • Bartsch O
        • Tympner KD
        • Schwinger E
        • Gorlin RJ.
        Mulvihill-Smith syndrome: case report and review.
        J Med Genet. 1994; 31: 707-711
        • de Silva DC
        • Wheatley DN
        • Herriot R
        • et al.
        Mulvihill-Smith progeria-like syndrome: a further report with delineation of phenotype, immunologic deficits, and novel observation of fibroblast abnormalities.
        Am J Med Genet. 1997; 69: 56-64
        • Ohashi H
        • Tsukahara M
        • Murano I
        • et al.
        Premature aging and immunodeficiency: Mulvihill-Smith syndrome?.
        Am J Med Genet. 1993; 45: 597-600
        • Stratakis CA
        • Raygada M.
        • et al.
        Carney complex.
        in: Adam MP Ardinger HH Pagon RA GeneReviews. University of Washington, Seattle, Seattle, WA2018
        • Kaltsas G
        • Kanakis G
        • Chrousos G
        • et al.
        Carney complex.
        in: Feingold KR Anawalt B Boyce A Endotext. MDText.com Inc., South Dartmouth, MA2018
      2. National Center for Biotechnology Information Genetic Testing Registry. Available at: https://www.ncbi.nlm.nih.gov/gtr/. Accessed May 2, 2019.

        • Kraemer KH
        • DiGiovanna JJ.
        Xeroderma pigmentosum. Seattle, WA: GeneReviews.
        University of Washington, Seattle, Seattle, WA2016
        • Pilarski R
        • Rai K
        • Cebulla C
        • Abdel-Rahman M.
        • et al.
        BAP1 tumor predisposition syndrome.
        in: Adam MP Ardinger HH Pagon RA GeneReviews. University of Washington, Seattle, Seattle, WA2016
        • Bondy CA.
        Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group.
        J Clin Endocrinol Metab. 2007; 92: 10-25
        • Allanson JE
        • Roberts AE
        • et al.
        Noonan syndrome.
        in: Adam MP Ardinger HH Pagon RA GeneReviews. University of Washington, Seattle, Seattle, WA2016
        • Schrier Vergano S
        • Santen G
        • Wieczorek D
        • Wollnik B
        • Matsumoto N
        • Deardorff MA
        • et al.
        Coffin-Siris syndrome.
        in: Adam MP Ardinger HH Pagon RA GeneReviews. University of Washington, Seattle, Seattle, WA2018
        • Sutton VR
        • van Bokhoven H.
        • et al.
        TP63-related disorders.
        in: Adam MP Ardinger HH Pagon RA GeneReviews. WA: University of Washington, Seattle, Seattle2015