skin abnormalities


Summary: Congenital structural abnormalities of the skin.

Top Publications

  1. Sharma V, Ruiz de Luzuriaga A, Waggoner D, Greenwald M, Stein S. Microphthalmia with linear skin defects: a case report and review. Pediatr Dermatol. 2008;25:548-52 pubmed publisher
    ..We present a patient with classic clinical and genetic findings of MLS syndrome and discuss the primary characteristics and management of this disorder...
  2. Fan J, Wang Y, Han B, Ji Y, Song H, Fan X. FOXL2 mutations in Chinese families with Blepharophimosis syndrome (BPES). Transl Res. 2011;157:48-52 pubmed publisher
    ..These new cases give additional support to the previously reported genotype-phenotype correlations and our findings have expanded the spectrum of known mutations of the FOXL2 gene...
  3. Haghighi A, Verdin H, Haghighi Kakhki H, Piri N, Gohari N, De Baere E. Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II. Mol Vis. 2012;18:211-8 pubmed
    ..Here, we report on a very severe form of BPES resulting from a missense mutation outside the forkhead domain...
  4. Morleo M, Pramparo T, Perone L, Gregato G, Le Caignec C, Mueller R, et al. Microphthalmia with linear skin defects (MLS) syndrome: clinical, cytogenetic, and molecular characterization of 11 cases. Am J Med Genet A. 2005;137:190-8 pubmed
    ..These patients made it possible to undertake mutation screening of candidate genes and may prove critical for the identification of the gene responsible for this challenging and intriguing genetic disease. ..
  5. Kutsche K, Werner W, Bartsch O, von der Wense A, Meinecke P, Gal A. Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp. Cytogenet Genome Res. 2002;99:297-302 pubmed
  6. List K, Haudenschild C, Szabo R, Chen W, Wahl S, Swaim W, et al. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene. 2002;21:3765-79 pubmed
    ..This study demonstrates that Matriptase/MT-SP1 has pleiotropic functions in the development of the epidermis, hair follicles, and cellular immune system. ..
  7. Kapur R, Tu E, Toyran S, Shah P, Vangveeravong S, Lloyd W, et al. Corneal pathology in microphthalmia with linear skin defects syndrome. Cornea. 2008;27:734-8 pubmed publisher
    ..To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome...
  8. Hobson G, Gibson C, Aragon M, Yuan Z, Davis Williams A, Banser L, et al. A large X-chromosomal deletion is associated with microphthalmia with linear skin defects (MLS) and amelogenesis imperfecta (XAI). Am J Med Genet A. 2009;149A:1698-705 pubmed publisher
    ..More than 50 additional genes were monosomic in this patient...
  9. Decock C, De Baere E, Bauters W, Shah A, Delaey C, Forsyth R, et al. Insights into levator muscle dysfunction in a cohort of patients with molecularly confirmed blepharophimosis-ptosis-epicanthus inversus syndrome using high-resolution imaging, anatomic examination, and histopathologic examination. Arch Ophthalmol. 2011;129:1564-9 pubmed publisher
    ..To study the basis of defective levator palpebrae superioris (LPS) function in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), an autosomal dominant eyelid malformation sometimes associated with ovarian dysfunction...

More Information


  1. List K, Szabo R, Wertz P, Segre J, Haudenschild C, Kim S, et al. Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. J Cell Biol. 2003;163:901-10 pubmed
    ..The data identify keratinocyte Matriptase/MT-SP1 as an essential component of the profilaggrin-processing pathway and a key regulator of terminal epidermal differentiation. ..
  2. Hoki Y, Araki R, Fujimori A, Ohhata T, Koseki H, Fukumura R, et al. Growth retardation and skin abnormalities of the Recql4-deficient mouse. Hum Mol Genet. 2003;12:2293-9 pubmed
    ..We speculate that the loss of Recql4 helicase activity results in the prematurely aged appearance observed in some RecQ helicase diseases. ..
  3. van der Velden J, Vreeburg M, Smeets E, Schrander Stumpel C, van Steensel M. Skin abnormalities in individuals with macrocephaly: Cowden disease from a dermatologist's point of view. Int J Dermatol. 2008;47 Suppl 1:45-8 pubmed publisher
    ..These findings combined with a (family) history of internal malignancy or a macrocephaly should raise the suspicion of PTHS, even in the absence of classical Cowden criteria. ..
  4. Wimplinger I, Morleo M, Rosenberger G, Iaconis D, Orth U, Meinecke P, et al. Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome. Am J Hum Genet. 2006;79:878-89 pubmed
    ..In summary, we suggest that disturbance of both OXPHOS and the balance between apoptosis and necrosis, as well as the X-inactivation pattern, may contribute to the variable phenotype observed in patients with MLS. ..
  5. Navarro C, De Sandre Giovannoli A, Bernard R, Boccaccio I, Boyer A, Genevieve D, et al. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet. 2004;13:2493-503 pubmed
    ..RD is thus one of the most deleterious laminopathies identified so far in humans caused by (primary or secondary) A-type Lamin defects and nuclear structural and functional alterations. ..
  6. Herrmann T, van der Hoeven F, Grone H, Stewart A, Langbein L, Kaiser I, et al. Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy. J Cell Biol. 2003;161:1105-15 pubmed
    ..These findings reveal a previously unknown, essential function of Fatp4 in the formation of the epidermal barrier. ..
  7. Enright F, Campbell P, Stallings R, Hall K, Green A, Sweeney E, et al. Xp22.3 microdeletion in a 19-year-old girl with clinical features of MLS syndrome. Pediatr Dermatol. 2003;20:153-7 pubmed
    ..We describe this patient with an Xp22.3 microdeletion to heighten awareness among dermatologists of this syndrome and to underscore the difficulties in diagnosing MLS syndrome...
  8. Paul T, Laohakunakorn P, Long B, Saul J. Complete elimination of incessant polymorphic ventricular tachycardia in an infant with MIDAS syndrome: use of endocardial mapping and radiofrequency catheter ablation. J Cardiovasc Electrophysiol. 2002;13:612-5 pubmed
    ..This report demonstrates the usefulness and safety of radiofrequency catheter ablation in an infant with polymorphic VT who was unresponsive to medical therapy. ..
  9. Wimplinger I, Rauch A, Orth U, Schwarzer U, Trautmann U, Kutsche K. Mother and daughter with a terminal Xp deletion: implication of chromosomal mosaicism and X-inactivation in the high clinical variability of the microphthalmia with linear skin defects (MLS) syndrome. Eur J Med Genet. 2007;50:421-31 pubmed
    ..Nonetheless, a non-random X-inactivation pattern in favor of activity of the wild-type X chromosome in the early blastocyte could also account for the apparent lack of any disease sign in this female...
  10. Cain C, Saul D, Attanasio L, Oehler E, Hamosh A, Blakemore K, et al. Microphthalmia with linear skin defects (MLS) syndrome evaluated by prenatal karyotyping, FISH and array comparative genomic hybridization. Prenat Diagn. 2007;27:373-9 pubmed
    ..To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome...
  11. Kumar A, Babu M, Raghunath A, Venkatesh C. Genetic analysis of a five generation Indian family with BPES: a novel missense mutation (p.Y215C). Mol Vis. 2004;10:445-9 pubmed
    ..The purpose of the present study was to carry out genetic analysis of BPES in a five-generation Indian family...
  12. Panteleyev A, Ahmad W, Malashenko A, Ignatieva E, Paus R, Sundberg J, et al. Molecular basis for the rhino Yurlovo (hr(rhY)) phenotype: severe skin abnormalities and female reproductive defects associated with an insertion in the hairless gene. Exp Dermatol. 1998;7:281-8 pubmed
    ..These results, together with previous studies of hr(rhY)/hr(rhY) mutant mice, suggest that the rhino Yurlovo (hr(rhY)) mutation represents a third and potentially more severe variation of the hairless phenotype. ..
  13. Kono T, Migita T, Koyama S, Seki I. Another observation of microphthalmia in an XX male: microphthalmia with linear skin defects syndrome without linear skin lesions. J Hum Genet. 1999;44:63-8 pubmed
    ..Our observation further supports the current hypothesis that the phenotypic variation of MLS syndrome represents tissue-different X inactivation rather than different genetic effects of two contiguous genes. ..
  14. Happle R, Daniels O, Koopman R. MIDAS syndrome (microphthalmia, dermal aplasia, and sclerocornea): an X-linked phenotype distinct from Goltz syndrome. Am J Med Genet. 1993;47:710-3 pubmed
    ..3. This new X-linked male-lethal trait should be distinguished from focal dermal hypoplasia that will be found to map elsewhere on the X-chromosome...
  15. Threadgill D, Dlugosz A, Hansen L, Tennenbaum T, Lichti U, Yee D, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science. 1995;269:230-4 pubmed
    ..The multiple abnormalities associated with EGFR deficiency indicate that the receptor is involved in a wide range of cellular activities. ..
  16. Prowse D, Lee D, Weiner L, Jiang N, Magro C, Baden H, et al. Ectopic expression of the nude gene induces hyperproliferation and defects in differentiation: implications for the self-renewal of cutaneous epithelia. Dev Biol. 1999;212:54-67 pubmed
  17. Liu X, Dangel A, Kelley R, Zhao W, Denny P, Botcherby M, et al. The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase. Nat Genet. 1999;22:182-7 pubmed
    ..They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism. ..
  18. Carroll J, Romero M, Watt F. Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Cell. 1995;83:957-68 pubmed
  19. Matsuki M, Yamashita F, Ishida Yamamoto A, Yamada K, Kinoshita C, Fushiki S, et al. Defective stratum corneum and early neonatal death in mice lacking the gene for transglutaminase 1 (keratinocyte transglutaminase). Proc Natl Acad Sci U S A. 1998;95:1044-9 pubmed
    ..Thus, these TGase 1 knockout mice may be a useful model for severe cases of LI. ..
  20. Ogata T, Wakui K, Muroya K, Ohashi H, Matsuo N, Brown D, et al. Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern. Hum Genet. 1998;103:51-6 pubmed
    ..This supports the notion that functional absence of the MLS gene caused by inactivation of the normal X chromosome plays a pivotal role in the development of MLS in patients with Xp22 monosomy. ..
  21. Luetteke N, Phillips H, Qiu T, Copeland N, Earp H, Jenkins N, et al. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev. 1994;8:399-413 pubmed
  22. Wapenaar M, Bassi M, Schaefer L, Grillo A, Ferrero G, Chinault A, et al. The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. Hum Mol Genet. 1993;2:947-52 pubmed
    ..Ten potential CpG-islands, representing candidate sites for genes, have been mapped within the 2.6 Mb region. Our data should greatly facilitate efforts aimed at cloning the genes for these developmental defects...
  23. Xiao J, Feng X, Di W, Peng Z, Li L, Chambon P, et al. Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors. EMBO J. 1999;18:1539-48 pubmed
    ..These events may underlie retinoid action in epidermal regeneration during wound healing. ..
  24. Takeda K, Takeuchi O, Tsujimura T, Itami S, Adachi O, Kawai T, et al. Limb and skin abnormalities in mice lacking IKKalpha. Science. 1999;284:313-6 pubmed
  25. Redondo P. [Vascular malformations (II). Diagnosis, pathology and treatment]. Actas Dermosifiliogr. 2007;98:219-35 pubmed
    ..The second part of this review is focused on the complementary diagnosis (imaging exams, pathology and accessory tests) and multidisciplinary and specific treatment based on the different groups. ..
  26. Yi R, Pasolli H, Landthaler M, Hafner M, Ojo T, Sheridan R, et al. DGCR8-dependent microRNA biogenesis is essential for skin development. Proc Natl Acad Sci U S A. 2009;106:498-502 pubmed publisher
    ..Our results underscore a specific importance of microRNAs in controlling mammalian skin development. ..
  27. Fryssira H, Papathanassiou M, Barbounaki J, Orfanou I, Lagona E, Paikos P. A male with polysyndactyly, linear skin defects and sclerocornea. Goltz syndrome versus MIDAS. Clin Dysmorphol. 2002;11:277-81 pubmed
    ..Clinical findings support the diagnosis of Goltz syndrome. The clinical picture of Goltz syndrome is compared with that of MIDAS syndrome...
  28. Levy N, Lopez Otin C, Hennekam R. Defective prelamin A processing resulting from LMNA or ZMPSTE24 mutations as the cause of restrictive dermopathy. Arch Dermatol. 2005;141:1473-4; author reply 1474 pubmed
  29. DeMaria D, Mejia Lopez E, Kelting S, Soukoulis V. A case of familial calcific aortic and mitral stenosis in association with hereditary sclerosing poikiloderma. Cardiovasc Pathol. 2016;25:195-9 pubmed publisher
    ..Multiple other family members had presented with similar cardiac and skin manifestations. Further research is needed to better understand the cardiac pathophysiology of this disease. ..
  30. Dinleyici E, Tekin N, Aksit M, Kilic Z, Adapinar B, Bozan G. Macrocephaly-Cutis marmorata telangiectatica congenita with atrial septal aneurysm and magnetic resonance imaging (MRI) findings. Pediatr Int. 2004;46:366-7 pubmed
  31. Lv D, Luo Y, Yang W, Cao L, Wen Y, Zhao X, et al. A novel single-base deletion in ROR2 causes atypical brachydactyly type B1 with cutaneous syndactyly in a large Chinese family. J Hum Genet. 2009;54:422-5 pubmed publisher
    ..To the best of our knowledge, the deletion represents the second ROR2 mutation associated with a BDB1-syndactyly phenotype...
  32. Virgili A, Tosti G, Bettoli V, Corazza M. Multiple congenital symmetric skin dimples. Dermatology. 2002;204:293-5 pubmed
    ..At a 3-year follow-up, the patient shows a normal psychophysical development. This appears to be the first case of a child presenting congenital, symmetric dimples in three different areas. ..
  33. Tartaglia M, Cotter P, Zampino G, Gelb B, Rauen K. Exclusion of PTPN11 mutations in Costello syndrome: further evidence for distinct genetic etiologies for Noonan, cardio-facio-cutaneous and Costello syndromes. Clin Genet. 2003;63:423-6 pubmed
    ..With our previous exclusion of PTPN11 mutations in CFC syndrome, these data suggest distinct genetic etiologies for Noonan, CFC and Costello syndromes. ..
  34. Sa H, Lee J, Woo K, Kim Y. A new method of medial epicanthoplasty for patients with blepharophimosis-ptosis-epicanthus inversus syndrome. Ophthalmology. 2012;119:2402-7 pubmed publisher
    ..Medial epicanthoplasty using the skin redraping method is an effective technique in the treatment of epicanthus inversus and telecanthus in patients with BPES, with excellent cosmetic outcomes. ..
  35. Belum V, Fontanilla Patel H, Lacouture M, Rodeck U. Skin toxicity of targeted cancer agents: mechanisms and intervention. Future Oncol. 2013;9:1161-70 pubmed publisher
    ..Emergent insights into the pathomechanisms involved and the use of this knowledge base to alleviate cutaneous adverse events are discussed. ..
  36. Yang X, Li W, Du J, Yuan S, He W, Zhang Q, et al. [Analysis of FOXL2 gene mutations in 5 families affected with blepharophimosis, ptosis and epicanthus inversus syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017;34:342-346 pubmed publisher
    ..Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The novel mutations have enriched the mutation spectrum of the FOXL2 gene. ..
  37. Vasan S, Jacob J, Seshadri M. Visual vignette. Albright-McCune syndrome. Endocr Pract. 2007;13:205 pubmed
  38. Casanova M, Bravo A, Martínez Palacio J, Fernández Aceñero M, Villanueva C, Larcher F, et al. Epidermal abnormalities and increased malignancy of skin tumors in human epidermal keratin 8-expressing transgenic mice. FASEB J. 2004;18:1556-8 pubmed
  39. Riedel F, Hormann K. [Plastic surgery of skin defects in the face. Principles and perspectives]. HNO. 2005;53:1020-36 pubmed
    ..The key concepts useful in flap choice and implementation are discussed. In addition, an overview of new developments in tissue engineering and gene therapy as they relate to facial plastic surgery is provided. ..
  40. Megarbane H, Cluzeau C, Bodemer C, Fraitag S, Chababi Atallah M, Megarbane A, et al. Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene. Am J Med Genet A. 2008;146A:2657-62 pubmed publisher
  41. Nuovo S, Passeri M, Di Benedetto E, Calanchini M, Meldolesi I, Di Giacomo M, et al. Characterization of endocrine features and genotype-phenotypes correlations in blepharophimosis-ptosis-epicanthus inversus syndrome type 1. J Endocrinol Invest. 2016;39:227-33 pubmed publisher
    ..This study highlights the importance of early recognition of BPES and emphasizes the need of personalized therapy and follow-up in female patients carrying distinct FOXL2 mutations. ..
  42. Salmon Hillbertz N, Isaksson M, Karlsson E, Hellmén E, Pielberg G, Savolainen P, et al. Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nat Genet. 2007;39:1318-20 pubmed
    ..FGFs play a crucial role in development, suggesting that the ridge and dermoid sinus are caused by dysregulation of one or more of the three FGF genes during development...
  43. Gagey Caron V, Stalder J, Barbarot S. [Basan's syndrome: Congenital absence of dermatoglyphs and milia]. Ann Dermatol Venereol. 2009;136:419-21 pubmed publisher
    ..This eruption revealed Basan's syndrome, a rare, autosomal dominant inherited dermatosis described as the association of profuse facial milia, acral bullae, absence of dermatoglyphs, and palmoplantar hypohydrosis. ..
  44. Duesbery N, Vande Woude G. BRAF and MEK mutations make a late entrance. Sci STKE. 2006;2006:pe15 pubmed
    ..This finding will undoubtedly stimulate further research into the function of these proteins in development and in both inherited and sporadic cancers. ..
  45. Leslie K, Levell N. Skin disease in mummies. Int J Dermatol. 2006;45:161-3 pubmed
  46. Schleifer S, Versteeg S, van Oost B, Willemse T. Familial footpad hyperkeratosis and inheritance of keratin 2, keratin 9, and desmoglein 1 in two pedigrees of Irish Terriers. Am J Vet Res. 2003;64:715-20 pubmed
    ..Mutations in the genes encoding keratin 2 and 9 as well as desmoglein 1 are highly unlikely to be the primary cause of familial footpad hyperkeratosis in Irish Terriers. ..
  47. Anthony S, Kateman H, Brand R, den Ouden A, Dorrepaal C, van der Pal de Bruin K, et al. Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort. Paediatr Perinat Epidemiol. 2005;19:135-44 pubmed
    ..For Mediterranean women, the largest and fastest growing group of immigrants in the Netherlands, this study demonstrated an increased risk of congenital malformations. ..
  48. Valdés Rodríguez R, Moncada González B, Rivera Rodríguez S, Aradillas García C, Hernández Rodríguez H, Torres Alvarez B. [Skin tags and Acanthosis nigricans: association with insulin resistance and overweight in Mexican children]. Gac Med Mex. 2011;147:297-302 pubmed
    ..The presence of skin tags and Acanthosis nigricans correlates with the presence of insulin resistance in children even in healthy weight patients and higher BMI. ..
  49. Obdeijn M, Offringa P, Bos R, Verhagen A, Niessen F, Roche N. Facial clefts and associated limb anomalies: description of three cases and a review of the literature. Cleft Palate Craniofac J. 2010;47:661-7 pubmed publisher
    ..This combination has, to our knowledge, not yet been reported. The literature about facial clefting and the amniotic band syndrome and the possible etiology of clefting and constrictions in these cases are discussed. ..
  50. Casanova J, Marti R, Baradad M, Egido R, Mascaro J. [Bart syndrome associated to lethal junctional epidermolysis bullosa (Herlitz form)]. Actas Dermosifiliogr. 2006;97:658-61 pubmed
    ..To our knowledge this is the second case that reports an association between Bart syndrome and lethal junctional epidermolysis bullosa and the first in which the results of immunofluorescence mapping are published. ..
  51. Schulz A, Albrecht B, Arici C, van der Burgt I, Buske A, Gillessen Kaesbach G, et al. Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome. Clin Genet. 2008;73:62-70 pubmed
  52. Chousta A, Ville D, James I, Foray P, Bisch C, Depardon P, et al. Pericallosal lipoma associated with Pai syndrome: prenatal imaging findings. Ultrasound Obstet Gynecol. 2008;32:708-10 pubmed publisher
    ..We underline the impact on parental counseling following prenatal detection of pericallosal lipoma. ..
  53. Bajaj Y, Dunaway D, Hartley B. Surgical approach for congenital midline cervical cleft. J Laryngol Otol. 2004;118:566-9 pubmed
    ..The operative findings, surgical excision and repair of the long vertical defect by Z-plasty are discussed in detail. The authors report a very satisfactory result following excision and Z-plasty closure of this rare congenital anomaly. ..