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E-IJD CASE REPORT
Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 421
Ectodermal dysplasia-skin fragility syndrome: A rare case report


1 Department of Dermatology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
2 Department of Pathology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr. Subhash Kashyap
Department of Dermatology, Indira Gandhi Medical College, Shimla, Himachal Pradesh - 171 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.160525

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   Abstract 

Ectodermal dysplasia/skin fragility syndrome (ED-SFS) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Only 12 cases of this rare genodermatosis have been reported so far. We present an unusual case of ED-SFS in a 12-year boy who was normal at birth but subsequently developed skin fragility, hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and abnormal sweating but no systemic abnormality.


Keywords: Chelitis, ectodermal dysplasia/skin fragility syndrome, granulosis rubra nasi, McGrath syndrome, palmoplantar keratoderma


How to cite this article:
Kashyap S, Shanker V, Sharma N. Ectodermal dysplasia-skin fragility syndrome: A rare case report. Indian J Dermatol 2015;60:421

How to cite this URL:
Kashyap S, Shanker V, Sharma N. Ectodermal dysplasia-skin fragility syndrome: A rare case report. Indian J Dermatol [serial online] 2015 [cited 2019 Jun 26];60:421. Available from: http://www.e-ijd.org/text.asp?2015/60/4/421/160525

What was known?

  • Ectodermal dysplasia/skin fragility syndrome (McGrath syndrome) is a rare genodermatosis characterized by features of both ectodermal dysplasia and skin fragility.
  • It present generally in neonatal period with diffuse erythroderma and chelitis and friction-induced blistering and later develops, palmoplantar keratoderma, hair, nail and sweating abnormalities.
  • Skin lesions occur due to loss-of-function mutations in the PKP1 gene.



   Introduction Top


Ectodermal dysplasia/skin fragility syndrome (ED-SFS), also known as McGrath syndrome, (MIM604536) is an autosomal recessive genodermatosis caused by loss of function mutation in the plakophilin gene 1 (PKP1). [1] It is characterized by features of both ectodermal dysplasia and skin fragility. [2] Since its first description in 1997, only 12 cases have been reported so far. [3] All but one reported cases presented in neonatal period with diffuse erythroderma and chelitis and friction induced blistering and later developed, palmoplantar keratoderma, hair, nail and sweating abnormalities. With limited number of case reports that too showing varied clinical features, exact role of plakophilin in the pathogenesis is not yet clearly delineated. [1],[4] We hereby present a 12-year boy who was normal at birth but subsequently developed features suggestive of this rare syndrome. In addition, he also had few features like, granulosis rubra nasi, retraction of ala nasi, hyperpigmented patch over right infraorbital area and inversion of nipples and gynacomastia which were not reported earlier.


   Case Report Top


A 12-year-old male child presented to us with short and sparse hairs over the scalp, eyebrows and eyelashes with trauma-induced blistering of skin which was first noted at the age of 3 months. Hair loss was progressive but skin blistering remained more or less constant but slight increased during summer months. Child was born to a non-consanguineous marriage with unremarkable antenatal history. His developmental milestones were normal. No other family member had similar symptoms. At 3 years of age parents noted nail deformities which was progressive. Palms and soles became rough with mild thickening. He had decreased sweating all over the body but hyperhidrosis on palms and soles, over the nose and the right cheek. Cutaneous examination showed lusterless, short and sparse scalp hair while eyebrows were completely absent and eyelashes were sparse. There was frontal bossing, nasal tip sweating and an erythematous plaque on right infraorbital area, and retracted ala nasi [Figure 1]a and b]. A bullous lesion was seen over the left ankle and fresh ruptured bulla on left thigh in addition to multiple crusted erosions and hyper pigmented macules were present over the trunk, groins, thighs and dorsa of hand and feet [Figure 1]c and d, [Figure 2]a and b]. Palms and soles showed hyperhidrosis and mild keratoderma. Dental examination revealed hypodontia of lower incisors, abnormal canines and delayed persistence of deciduas teeth. Nails were slightly curved (koilonychia) with anonychia and dystrophy in some nails [Figure 2]c and d]. Nikolsky's sign was negative.
Figure 1: (a) Clinical image of face and head showing short and sparse hair over scalp, eyebrows, frontal bossing, and retracted ala nasi. (b) Closer view showing granulosis rubra nasi. (c and d) Photograph showing multiple crusted erosions with hyper pigmented macules seen over the trunk, groins and thighs

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Figure 2: (a) A Bullous lesion seen over the left ankle. (b) A fresh ruptured bulla on left thigh. (c) Koilonychias left great toe and anonychia small toe of same side. (d) Palms and soles showing hyperhidrosis and mild keratoderma

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His routine investigations, electrocardiogram (ECG) and chest X-rays were normal. Histopathological examination showed blister formation in stratum spinosum with occasional acantholytic cells [Figure 3]. Immunostaining for IgG and IgA was negative. Genetic studies could not be afforded by the patient. Based on the spectrum of the clinical features a diagnosis of ectodermal dysplasia-skin fragility syndrome was made. Parents were counseled about the benign nature of the disease, proper skin care and regular follow up.
Figure 3: Keratinized stratified squamous epithelium revealing blister formation in stratum spinosum with occasional acantholytic cells (H and E, ×40)

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   Discussion Top


Congenital and hereditary disorders of skin adhesion are collectively grouped under the umbrella of epidermolysis bullosa (EB), and these diseases are further separated depending upon the level of intracutaneous cleavage. ED-SFS is classified as a specific suprabasal form of epidermolysis bullosa simplex. [5] It occurs due to loss of function mutation in loss of function mutation in the plakophilin gene PKP1. PKP is a structural component of desmosomes, cell-cell adhesion complexes found in stratified squamous epithelia, myocardium, meninges, and parts of lymph nodes. [6] In skin, PKP1 expression is confined mainly to suprabasal keratinocytes and the outer root sheath of hair follicles. [7] Two isoforms of PKP1, 1a and 1b, have been described. [8] PKP1a is expressed in both desmosomes and nuclei, whereas PKP1b is expressed only in nuclei. Currently, the specific biologic significance of the two isoforms is unknown. [9]

Skin lesions were first noted at birth in all but one individual. [10] Affected neonates initially exhibit diffuse erythroderma and skin fragility (blisters, erosions) at areas of friction and trauma. [8] Hair abnormalities such as partial hypotrichosis to complete hairlessness, woolly hair as well as nail dystrophies are seen in all reported cases. Chronic perioral inflammation (cheilitis) with cracking and palmoplantar keratodermas with fissures are seen in majority of cases but not all. [8] Various other clinical features noted in earlier case reports include short stature, astigmatism, growth retardation, pruritus, dental caries, patent foramen ovale, pneumonia, lenticular opacities, failure to thrive, recurrent skin infections, follicular hyperkeratosis and one case had acrodermatitis enteropathica which responded to zinc supplementation. [4]

Clinical evaluation of reported cases revealed variability in the extent of the alopecia and the degree of disability associated with the skin fissures and erosions. Our case also showed varied clinical profile but hair, teeth and dental anomalies with palmoplantar keratodermas and skin fragility were consistent with the diagnosis of ED-SFS. Additional features not reported earlier included, nonfollicular papules over the scalp, nasal sweating (granulosis rubra nasi), retraction of ala nasi, hyperpigmented patch over right infraorbital area, inversion of nipples and gynacomastia. Increased sweating of palms and soles and nasal tip were due to compensatory hyperhidrosis. Only other case that was normal at birth was reported by Hamada et al., [10] at the age of 42 years with no serious disability, so prognosis is expected to be good in such cases like this case.

Clinical diversity in ED-SFS probably reflects the consequences of the individual PKP1 mutations on the levels of functional PKP1 protein. Most of the mutations seen are splice-site mutations resulting in exon skipping or cryptic splicing rather than complete ablation of plakophilin 1. [3] With few cases reported with varied clinical profile, further genetic studies are needed to establish exact pathogenesis in this rare syndrome.

Histopathological findings include epidermal hyperplasia with cell-cell separation that varies from a widening of intercellular spaces to severe acantholysis in the stratum spinosum. Aggregation of keratin filaments (e.g. dyskeratosis) is also seen. [3] Histopathological examination in this case showed blister formation in stratum spinosum with occasional acantholytic cells similar to previous case reports. [4]

Our differential diagnosis included Atrichia with popular lesions (APL), which was excluded by presence of other clinical features and absence of keratinous cysts. Porphyria and Kindler syndrome were excluded by lack of photosensitivity, scarring, atrophy, and sclerodermoid changes.

To best of our knowledge this is the second case of ED-SFS reported from India. This case is also reported to highlight the clinical diversity involving this syndrome.



 
   References Top

1.
Ersoy-Evans S, Erkin G, Fassihi H, Chan I, Paller AS, Sürücü S, et al. Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1. J Am Acad Dermatol 2006;55:157-61.  Back to cited text no. 1
    
2.
Nallanchakrava S. Oral rehabilitation of a patient with ectodermal dysplasia with prosthodontics treatment. Indian J Dermatol 2013;58:241.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Tanaka A, Lai-Cheong JE, Café ME, Gontijo B, Salomão PR, Pereira L, et al. Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families. Br J Dermatol 2009;160:692-7.  Back to cited text no. 3
    
4.
Adhe VS, Dongre AM, Khopkar US. Ectodermal dysplasia-skin fragility syndrome. Indian J Dermatol Venereol Leprol 2011;77:503-6.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.
Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, et al. The classification of inherited epidermolysis bullosa (EB): Report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol 2008;58:931-50.  Back to cited text no. 5
    
6.
South AP. Plakophilin 1: An important stabilizer of desmosomes. Clin Exp Dermatol 2004;29:161-7.  Back to cited text no. 6
    
7.
Moll I, Kurzen H, Langbein L, Franke WW. The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors. J Invest Dermatol 1997;108:139-46.  Back to cited text no. 7
    
8.
McGrath JA, Mellerio JE. Ectodermal dysplasia-skin fragility syndrome. Dermatol Clin 2010;28:125-9.  Back to cited text no. 8
    
9.
Sobolik-Delmaire T, Katafiasz D, Wahl JK 3 rd . Carboxyl terminus of plakophilin 1 recruits to its plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly. J Biol Chem 2006;281:16962-70.  Back to cited text no. 9
    
10.
Hamada T, South AP, Mitsuhashi Y, Kinebuchi T, Bleck O, Ashton GH, et al. Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1. Exp Dermatol 2002;11:107-14.  Back to cited text no. 10
    

What is new?

  1. Ectodermal dysplasia/skin fragility syndrome may present with delayed onset and cheilitis can be absent.
  2. There can be additional features like nonfollicular papules over the scalp, nasal sweating (granulosis rubra nasi), retraction of ala nasi, hyperpigmented patch over right infraorbital area and inversion of nipples and gynacomastia.
  3. As there are only few cases reported with varied clinical profile, further genetic studies are needed to establish exact pathogenesis in this rare syndrome.


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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