Atrophic Skin Patches With Abnormal Elastic Fibers as a Presenting Sign of the MASS Phenotype Associated With Mutation in the Fibrillin 1 Gene | Dermatology | JAMA Dermatology | JAMA Network
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Case Report/Case Series
August 2014

Atrophic Skin Patches With Abnormal Elastic Fibers as a Presenting Sign of the MASS Phenotype Associated With Mutation in the Fibrillin 1 Gene

Author Affiliations
  • 1Department of Dermatology, Rambam Health Care Campus, Haifa, Israel
  • 2Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
  • 3Medical Genetics Institute, Rambam Health Care Campus, Haifa, Israel
JAMA Dermatol. 2014;150(8):885-889. doi:10.1001/jamadermatol.2013.10036

Importance  Marfan syndrome (MFS) is a dominantly inherited disorder of connective tissue caused by mutations in the fibrillin 1 gene (FBN1). The most common skin finding in MFS is striae distensae. Particular individuals referred for suspected MFS who do not completely fulfill the MFS diagnostic criteria are classified as having a MASS phenotype. The acronym represents the following manifestations: a prolapsed mitral valve, myopia, aortic root enlargement, and skeletal and skin manifestations. Mutations in FBN1 have been shown to be associated in some cases with the MASS phenotype. Skin manifestations may be an important clue to the diagnosis of these disorders.

Observations  We studied a patient referred for unusual atrophic skin patches on the buttocks. Results of histopathological examination and electron microscopy demonstrated markedly abnormal elastic fibers. Subsequent medical genetics evaluation led ultimately to the diagnosis of the MASS phenotype and the discovery of an underlying FBN1 mutation.

Conclusions and Relevance  Although the clinical suspicion and diagnosis of MFS and related disorders are usually established by its main associated clinical features, including ophthalmologic, skeletal, and vascular involvement, clinicians should be aware of the associated skin manifestations, including unusual atrophic patches with abnormal elastic fibers that can sometimes be the first noted sign of the genetic disorder.

Marfan syndrome (MFS) is a life-threatening autosomal dominant disorder of connective tissue. Chief manifestations include proximal aortic aneurysm, dislocation of the ocular lens, and bone overgrowth.1 Mutations in the FBN1 gene (OMIM 134797), which encodes the matrix protein fibrillin 1, are identified in more than 90% of patients presenting with classic MFS.2,3 The most common skin findings in MFS are striae, especially at unusual sites.4 Histologic findings support the view that striae distensae are scars.5

Some individuals referred for suspected MFS exhibit evidence of a connective tissue disorder but do not completely fulfill MFS diagnostic criteria. These cases have been given the acronym MASS phenotype (OMIM 604308), which represents the following manifestations: mitral valve prolapse, myopia, borderline and nonprogressive aortic enlargement, and nonspecific skin and skeletal features. Similar to MFS, the most common skin alterations in MASS phenotype are also striae.6 Furthermore, mutations in FBN1 have been shown to be associated in some cases with the MASS phenotype.7

We recently studied a patient referred for atrophic anetoderma-like lesions on the buttocks with histopathological and ultrastructural evidence of markedly abnormal elastic fibers. These findings led to the diagnosis of the MASS phenotype with an underlying FBN1 mutation. We further discuss this unusual skin finding not previously reported in patients with MFS or the MASS phenotype.

Report of a Case

Dermatologic Evaluation

A man in his late 50s was referred for atrophic patches on the buttocks. One atrophic patch had been present on the left buttock since 15 years of age. The second patch appeared on the right buttock some months prior and was noted to be painful (Figure 1). His medical history was unremarkable. Skin examination revealed 2 erythematous large atrophic patches on both buttocks and an additional smaller skin-colored atrophic patch on the left buttock. The older erythematous patch on the left buttock was 10 cm in diameter, whereas the newer one on the right buttock measured 5 cm in diameter (Figure 1). All 3 lesions were soft and nontender on palpation.

Figure 1.  Clinical Presentation of an Atrophic Skin Lesion
Clinical Presentation of an Atrophic Skin Lesion

An erythematous atrophic patch on the right buttock.

Skin biopsy specimens were obtained from the centers of the 2 larger lesions. The biopsy from the large lesion on the left buttock revealed large eosinophilic colloidlike aggregations in the papillary dermis (Figure 2A). Higher magnification revealed clumps of curly eosinophilic fibers within the colloidlike aggregates. In addition, we noted an apparent increase in the number of small blood vessels throughout entire dermis. Elastic tissue stain demonstrated large clumps of curly elastic fibers within the colloidlike aggregates (Figure 2B). In the dermis, large areas were devoid of elastic fibers with occasional short “chopped” thick elastic fibers and increased numbers of small blood vessels. Some bundles of densely packed curly elastic fibers were seen in the lower dermis. The biopsy from the lesion on the right buttock demonstrated an increased number of small blood vessels throughout the dermis. A Verhoeff–van Gieson elastic tissue stain revealed an increased number of thick elastic fibers. Higher magnification demonstrated short or chopped elastic fibers and bundles and aggregates of thick wavy elastic fibers (Figure 2C). Results of the Congo red and von Kossa stains did not show amyloid or calcium, respectively.

Figure 2.  Histopathological Examination of the Atrophic Skin Lesion
Histopathological Examination of the Atrophic Skin Lesion

A, A biopsy specimen obtained from the atrophic lesion on the left buttock. The epidermis is normal looking, and colloidlike aggregates in the papillary dermis consist predominantly of dense aggregates of eosinophilic fibers. An increased number of small blood vessels is also present (hematoxylin-eosin, original magnification ×200). B, An elastic tissue stain demonstrates that the colloidlike aggregates in the upper dermis are made largely of dense round aggregates of curly elastic fibers (Verhoeff–van Gieson [VVG] stain, original magnification ×200). C, A biopsy specimen obtained from the atrophic lesion on the right buttock. Short elastic fibers are seen along with thick and wavy irregular bundles of elastic fibers (VVG stain, original magnification ×400).

A biopsy specimen for electron microscopy was obtained from the uninvolved normal-looking skin on the buttock. The ultrastructural study performed as previously described8 revealed normal-looking collagen fibrils intermingled with abnormal-looking fragmented elastic fibers (Figure 3A). The elastic fibers had the appearance of numerous cracks and holes at their peripheries, which produced a network reminiscent of a cobweb (Figure 3). At a higher magnification, numerous fibrils were present at the borders of the cobweblike formations (Figure 3B). Owing to the marked histopathological and ultrastructural abnormalities of the elastic fibers observed, a medical genetics consultation was requested for evaluation of a possible underlying disorder of connective tissue.

Figure 3.  Electron Microscopy of an Atrophic Skin Lesion
Electron Microscopy of an Atrophic Skin Lesion

A, Electron microscopy shows normal-looking collagen fibrils (C) and 2 abnormal-looking fragmented elastic fibers (E) with the appearance of cracks and holes at their peripheries, along with numerous microfibrils (original magnification ×20 000). B, Higher-magnification electron microscopy shows an elastic fiber with the appearance of numerous peripheral cracks, holes, and microfibrils, resulting in a cobweblike appearance (original magnification ×30 000). F indicates microfibrils.

Medical Genetics Evaluation

The patient reported a history of clumsiness and recurrent falls during childhood but no significant joint laxity, joint dislocations, or fractures. He was diagnosed with mild scoliosis during his teenage years but had not needed any corrective measures. Bruising and scar formation were normal. He also reported having high myopia since childhood. His parents were nonconsanguineous and both died of heart disease late in the seventh decade of life. Results of the physical examination revealed a slender man (Figure 4A) with nondysmorphic facial features. Oral examination revealed a single uvula, normal palate, and missing teeth due to poor oral hygiene, although no periodontal disease was noted. No pectus carinatum or excavatum deformity was found, although a mild bone dysplasia was noted at the clavicles and ribs. Joint hypermobility was noted at the fingers, although thumb and wrist signs were negative for MFS. At the elbows, contractures were observed (Figure 4B), and the patient was unable to extend his elbows. At the back, a mild kyphoscoliosis was noted. In addition to the 2 atrophic patches on the buttocks, the skin examination revealed loss of subcutaneous fat, reduced muscle mass, no striae atrophica, normal scars, and dry nonhyperextensible skin. An ophthalmological examination confirmed high myopia and excluded lens and retinal abnormalities. An echocardiogram demonstrated mild prolapse of the mitral valve and a borderline aortic root enlargement (aortic root diameter, 37 mm; reference range, 20-37 mm). Based on the clinical findings, the patient was given a diagnosis of Marfan-like syndrome or the MASS phenotype. Because the MASS phenotype was reported to be sometimes associated with mutations in the FBN1 gene,9 gene sequencing was completed and identified a c.3422C>T; p.Pro1141Leu missense mutation in exon 27 of the FBN1 gene.

Figure 4.  Clinical Features of a Patient With the MASS Phenotype
Clinical Features of a Patient With the MASS Phenotype

The phenotype is named from the following features: mitral valve prolapse, myopia, borderline and nonprogressive aortic enlargement, and nonspecific skin and skeletal features. A, This patient has characteristic slender habitus and loss of subcutaneous fat. No pectus deformity of the anterior chest wall is seen. B, Elbow contractures are noted.


The atrophic skin patches in our patient clinically resembled antedoderma and middermal elastolysis. Both defects are characterized by a loss of elastic tissue without an increased amount of abnormal elastic fibers, as in our patient. Increased amounts of elastic tissue may be seen in solar elastosis, pseudoxanthoma elasticum, elastosis perforans serpiginosa, and isolated elastomas. The non–sun-exposed location of the lesions, the lack of calcium with a von Kossa stain, the lack of transepidermal elimination, and the clinical presentation, respectively, precluded these possibilities.

The most common skin manifestation of MFS and the MASS phenotype are striae.4,6 Striae distensae consist of bands of thin, wrinkled skin that are red, then purple, and finally white. The histopathological features of striae associated with MFS and other conditions are similar: the epidermis is thin and flattened, and the upper dermis is decreased in thickness and characterized by straight thin collagen bundles arranged parallel to the skin along with elastic fibers that are arranged similarly. The elastic fibers are present in greater quantity than in the surrounding skin, possibly as dense bundles of parallel fibers.5 Below this zone, a localized absence of elastic fibers may be noted, and in the borders between the striae and normal skin, curled, broken, and reticular elastic fibers are sometimes evident.5 For these reasons, striae distensae are considered scars. In the present case, the biopsy findings of the specimens taken from the centers of the lesions did not show the characteristic histopathological features or structure of striae distensae, and the ultrastructural study demonstrated elastic fibers with markedly abnormal structure.

The ultrastructural findings in this case resembled those described in the normal-looking skin of a 15-year-old girl with MFS.10 The main finding in the younger patient was fragmentation of elastic fibers at their peripheries with subdivision into many fine fibers, ultimately giving them a cobweblike appearance.10 This ultrastructural resemblance encouraged us to pursue a medical genetics evaluation, which resulted in the diagnosis of the MASS phenotype and a mutation in the FBN1 gene.

The first descriptions of the MASS phenotype appeared in the literature more than 20 years ago, when Glesby and Pyeritz11 noticed that many patients presenting with various manifestations of MFS, including long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse, and mild dilatation of the aortic root, could not undergo precise classification. Owing to lack of availability of genetic and biochemical testing at the time, the authors suggested that these patients should be considered to have an overlapping heritable connective tissue disorder. They further suggested the acronym to signify the involvement of the mitral valve, aorta, skeleton, and skin. Despite the time elapsed since its introduction, descriptions of patients with the MASS phenotype due to mutations in FBN1 are rare, and genotype-phenotype descriptions remain limited. Thus, the acronym primarily lingers as a diagnosis for those who do not meet the requirements for a complete MFS diagnosis. In addition, this diagnosis can be established only for individuals 20 years or older, because distinguishing the MASS phenotype from “emerging” MFS in an isolated individual, especially one undergoing assessment during childhood, is difficult.12 Reported dermatologic manifestations of MFS are very limited, probably because of the more prominent, treatable, and morbidity-related cardiovascular and ophthalmologic manifestations of MFS. However, the presence of striae distensae has been reported repeatedly in MFS and is considered a characteristic systemic feature.4 Additional reported findings include hernias9 and paucity of muscle and fat tissue stores despite adequate caloric intake, as was observed in our patient.

Fibrillin is the major constitutive element of extracellular microfibrils and has widespread distribution in elastic and nonelastic connective tissue throughout the body. Generally, fibrillin microfibrils are found at the periphery of elastic fibers and have been associated with the following 2 physiologically vital functions: providing a supportive scaffold for the deposition of elastin during elastogenesis and regulating the bioavailability of the transforming growth factor β superfamily.13,14 In addition to MFS and the MASS phenotype, mutations in the FBN1 gene have been implicated in familial ectopia lentis, geleophysic dysplasia, Weill-Marchesani syndrome, acromicric dysplasia, and stiff skin syndrome. Among these FBN1-associated syndromes, the following 2 general phenotypes emerge: Marfan-like features and features from the acromelic dysplasia family (ie, short stature and joint contractures). With respect to Marfan-spectrum disorders, missense mutations in the FBN1 gene that do not affect conserved regions or impair structural competency are assumed to yield the mildest phenotype. Likewise, in our patient, the identifying mutation was described in the literature only once in a cohort with MFS.15 However, because no clinical description is available, the extent of phenotypic severity cannot be juxtaposed to our patient.


Although the diagnosis of inherited disorders of connective tissue is usually established by the skeletal, vascular, and ophthalmologic manifestations, clinicians should be aware of the associated skin findings. These findings include unusual atrophic patches with abnormal elastic fibers, which can sometimes be the first noted sign of the genetic disorder.

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Article Information

Accepted for Publication: November 27, 2013.

Corresponding Author: Eyal Reinstein, MD, PhD, Medical Genetics Institute, Rambam Health Care Campus, PO Box 9602, Haifa, Israel 31096 (

Published Online: April 16, 2014. doi:10.1001/jamadermatol.2013.10036.

Author Contributions: Drs Bergman and Reinstein had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Bergman, Reinstein.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Bergman, Gescheidt-Shoshany, Pimienta, Reinstein.

Critical revision of the manuscript for important intellectual content: Nevet, Gescheidt-Shoshany, Pimienta, Reinstein.

Obtained funding: Bergman.

Administrative, technical, or material support: Bergman, Nevet, Gescheidt-Shoshany, Reinstein.

Study supervision: Bergman, Reinstein.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported in part by Rambam Atidim Academic Excellence Program (Dr Reinstein).

Role of the Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Ho  NC, Tran  JR, Bektas  A.  Marfan’s syndrome.  Lancet. 2005;366(9501):1978-1981.PubMedGoogle ScholarCrossref
Comeglio  P, Johnson  P, Arno  G,  et al.  The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations.  Hum Mutat. 2007;28(9):928. doi:10.1002/humu.9505.PubMedGoogle ScholarCrossref
Rommel  K, Karck  M, Haverich  A,  et al.  Identification of 29 novel and nine recurrent fibrillin-1 (FBN1) mutations and genotype-phenotype correlations in 76 patients with Marfan syndrome.  Hum Mutat. 2005;26(6):529-539.PubMedGoogle ScholarCrossref
Ledoux  M, Beauchet  A, Fermanian  C, Boileau  C, Jondeau  G, Saiag  P.  A case-control study of cutaneous signs in adult patients with Marfan disease: diagnostic value of striae.  J Am Acad Dermatol. 2011;64(2):290-295.PubMedGoogle ScholarCrossref
Miller  MK, Naik  MS, Nousari  CH, Friedman  RJ, Heilman  ER. Degenerative diseases and perforating disorders. In: Elder  DE, Elentisas  R, Johnson  BL, Murphy  GF, Xu  G, eds.  Lever's Histopathology of the Sin. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:389-405.
Tocchioni  F, Ghionzoli  M, Pepe  G, Messineo  A.  Pectus excavatum and MASS phenotype: an unknown association.  J Laparoendosc Adv Surg Tech A. 2012;22(5):508-513.PubMedGoogle ScholarCrossref
Wilson  BT, Jensen  SA, McAnulty  CP, Brennan  P, Handford  PA.  Juvenile idiopathic arthritis, mitral valve prolapse and a familial variant involving the integrin-binding fragment of FBN1 Am J Med Genet. 2013;161A(8):2047-2051. doi:10.1002/ajmg.a.36011. PubMedGoogle ScholarCrossref
Goldsmith  T, Fuchs-Telem  D, Israeli  S,  et al.  The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12.  Exp Dermatol. 2013;22(4):251-254.PubMedGoogle ScholarCrossref
Loeys  BL, Dietz  HC, Braverman  AC,  et al.  The revised Ghent nosology for the Marfan syndrome.  J Med Genet. 2010;47(7):476-485.PubMedGoogle ScholarCrossref
Tsuji  T.  Marfan syndrome: demonstration of abnormal elastic fibers in skin.  J Cutan Pathol. 1986;13(2):144-153.PubMedGoogle ScholarCrossref
Glesby  MJ, Pyeritz  RE.  Association of mitral valve prolapse and systemic abnormalities of connective tissue: a phenotypic continuum.  JAMA. 1989;262(4):523-528.PubMedGoogle ScholarCrossref
Stheneur  C, Tubach  F, Jouneaux  M,  et al.  Study of phenotype evolution during childhood in Marfan syndrome to improve clinical recognition [published online September 5, 2013].  Genet Med. doi:10.1038/gim.2013.123.Google Scholar
Rybczynski  M, Bernhardt  AM, Rehder  U,  et al.  The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome.  Am J Med Genet A. 2008;146A(24):3157-3166.PubMedGoogle ScholarCrossref
Akhurst  RJ.  TGF beta signaling in health and disease.  Nat Genet. 2004;36(8):790-792.PubMedGoogle ScholarCrossref
Yuan  B, Thomas  JP, von Kodolitsch  Y, Pyeritz  RE.  Comparison of heteroduplex analysis, direct sequencing, and enzyme mismatch cleavage for detecting mutations in a large gene, FBN1 Hum Mutat. 1999;14(5):440-446.PubMedGoogle ScholarCrossref