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Table of Contents 
CASE REPORT
Year : 2020  |  Volume : 65  |  Issue : 6  |  Page : 519-521
Restrictive dermopathy – A rare congenital skin disorder


1 Department of Neonatology, Kalawati Saran Children Hospital and Lady Hardinge Medical College, New Delhi, India
2 Department of Dermatology, Lady Hardinge Medical College, New Delhi, India
3 Department of Pathology, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research, New Delhi, India

Date of Web Publication23-Oct-2020

Correspondence Address:
Sarita Sanke
Room No 220, HSB Hostel, Lady Hardinge Medical College, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_554_18

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   Abstract 


Restrictive dermopathy is a rare, autosomal recessive, lethal congenital skin disorder. This congenital genodermatosis could be mistaken for various other similar skin disorders. Diagnosis is a must in the context of genetic counseling for the subsequent pregnancy. We herein report a preterm male neonate with restrictive dermopathy, with additional feature of multiple bone fractures.


Keywords: Congenital multiple contractures, fetal akinesia/hypokinesia deformation sequence, restrictive dermopathy


How to cite this article:
Viraraghavan V R, Sanke S, Mendiratta V, Dewan A, Kumar A, Pangti R. Restrictive dermopathy – A rare congenital skin disorder. Indian J Dermatol 2020;65:519-21

How to cite this URL:
Viraraghavan V R, Sanke S, Mendiratta V, Dewan A, Kumar A, Pangti R. Restrictive dermopathy – A rare congenital skin disorder. Indian J Dermatol [serial online] 2020 [cited 2020 Dec 4];65:519-21. Available from: https://www.e-ijd.org/text.asp?2020/65/6/519/298924





   Introduction Top


Restrictive dermopathy is a rare, autosomal recessive, lethal congenital skin disorder. Clinical diagnosis is very crucial for this disorder as it has an autosomal recessive pattern of inheritance and majority of the babies die very soon after birth, making a later pathological diagnosis difficult. Diagnosis is a must in the context of genetic counseling for the subsequent pregnancy and antenatal diagnosis can be made if there is a strong suspicion.


   Case Report Top


We report a preterm (32 weeks) male neonate, born to a second-degree consanguineous parentage. He was an IUGR (intrauterine growth retardation) baby of birth weight 1000 g.

Birth history was otherwise unremarkable. The patient had rigid tense shiny skin with scaling, prominent subcutaneous veins and a deep fissure at the anterior neck. Other dysmorphic features included a wide open anterior fontanelle, sparse eyebrows and eyelashes small upturned nose, hypertelorism, small mouth, retrognathia, dysplastic ears, multiple contractures in all the joints, scrotal edema, thin tapering fingers with long nails, natal teeth, and rocker bottom feet. The characteristic facies with multiple joint contractures are illustrated in [Figure 1]. Anthropometry revealed weight, length, and head circumference to be below the third centile for gestation. Roentgenogram revealed multiple fractures involving the clavicle and humerus. Ultrasonography of cranium, abdomen, and kidney were all within normal limits. The baby survived for a duration of 41 days. Skin biopsy revealed a smooth epidermis, which showed complete loss of rete ridges and a flat dermo-epidermal junction [Figure 2]. Dermis was thinned out and showed deposition of collagen in compact parallel bundles, which was positive on Masson's trichrome stain [Figure 3]. The elastin fibers were markedly reduced in the dermis.
Figure 1: The characteristic facies and the fixed flexion deformities involving all the joints

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Figure 2: Skin histopathology showing hyperkeratosis, flattened rete ridges, thinned out dermis with dense collagenization, and prominent subcutis (H and E, ×100)

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Figure 3: Masson's trichrome stain highlighting the collagen in dermis (×40)

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On genetic analysis (by clinical exome sequencing at University of Texas (UT) Southwestern Medical Center, Dallas, TX), both the parents harbored heterozygous c.1085insT (p. Leu362PhefsX19) mutation in ZMPSTE24 . Unfortunately, DNA of the affected child was not available; hence, it could not be analyzed.


   Discussion Top


This lethal congenital genodermatosis characterized by a rigid skin forms a part of fetal akinesia/hypokinesia deformation sequence, which results in multiple anomalies. Some features that are consistently seen with this disorder include consanguinity, preterm, premature rupture of membranes, IUGR, respiratory distress secondary to a tight chest wall, wide open anterior fontanelle, typical shiny rigid skin with fissures, small mouth, hypertelorism, dysplastic ears, dysplastic clavicles, and arthrogryposis multiplex congenita.[1] All these features were noted in this baby also. The feature that was deviant from the already reported cases of restrictive dermopathy was the multiple bone fractures. This finding has not been reported previously. A variety of histopathological findings have been described in cases of restrictive dermopathy.[2],[3],[4],[5] These include a thin dermis composed of dense horizontally arranged bundles of collagen, paucity and lack of maturation in skin appendages, markedly reduced elastic fibers, and a straight dermo-epidermal border. Intraepidermal and subepidermal bullae have also been described.[4],[6] Stiff or taut skin and joint contractures may also be seen in infantile hyalinosis and Winchester syndrome, which are characterized by deposition of hyaline material and mucopolysaccharides, respectively.[7] These were absent in the present case. The various other skin disorders, which are easily confused with restrictive dermopathy, are illustrated in [Table 1].
Table 1: Differential diagnosis for restrictive dermopathy

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The mutation in the gene loci ZMPSTE24 encoding a zinc metalloproteinase or LMNA/C on chromosome 1, which are both involved in the same processing pathway, is responsible for this congenital disorder of skin differentiation.[8]LMNA encodes A-type lamins which form nuclear lamina and play a role in regulation of gene expression, chromatin organization, DNA replication, and repair.[9],[10]ZMPSTE24 is responsible for the posttranslational A-type lamin maturation. Antenatal diagnosis can be attempted at around 18–22 weeks by looking for decreased fetal movements and joint contractures. Skin biopsy can be done only after 22 weeks as the typical features develop after this time. All these antenatal findings are however very nonspecific.[4] Hence, a mutation analysis from chorionic villous sampling/amniocentesis is a reliable method of choice for prenatal diagnosis in such cases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgments

The authors thank Dr. Abhimanyu Garg (5) and Dr. Seema Kapoor (Director Professor, Department of Pediatrics, Maulana Azad Medical College, New Delhi, India) for performing the genetic analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Verloes A, Mulliez N, Gonzales M, Laloux F, Hermanns-Le T, Pierard GE, et al . Restrictive dermopathy, a lethal form of arthrogryposis multiplex with skin and bone dysplasias: Three new cases and review of the literature. Am J Med Genet 1992;43:539-47.  Back to cited text no. 1
    
2.
Hou JW, Mai CF. Restrictive dermopathy in two sisters. Chang Gung Med J 2003;26:510-4.  Back to cited text no. 2
    
3.
Lu CS, Wu SC, Hou JW, Chu CP, Tseng LL, Lue HC. Restrictive dermopathy: Report of two siblings. Pediatr Neonatol 2013;54:198-201.  Back to cited text no. 3
    
4.
Mau U, Kendziorra H, Kaiser P, Enders H. Restrictive dermopathy: Report and review. Am J Med Genet 1997;71:179-85.  Back to cited text no. 4
    
5.
Smigiel R, Jakubiak A, Esteves-Vieira V, Szela K, Halon A, Jurek T, et al . Novel frameshifting mutations of the ZMPSTE24 gene in two siblings affected with restrictive dermopathy and review of the mutations described in the literature. Am J Med Genet 2010;152A:447-52.  Back to cited text no. 5
    
6.
Bidier M, Salz M, Meyburg J, Elbe-Bürger A, Lasitzschka F, Hausser I, et al . Restrictive dermopathy: Four case reports and structural skin changes. Acta Derm Venereol 2018;98:807-8.  Back to cited text no. 6
    
7.
Nijsten TEC, De Moor A, Colpaert CG, Robert K, Mahieu LM, Lambert J. Restrictive dermopathy: A case report and a critical review of all hypotheses of its origin. Pediatr Dermatol 2002;19:67-72.  Back to cited text no. 7
    
8.
Navarro C, De Sandre-Giovannoli A, Bernadr R, Boccaccio I, Boyer A, Geneviève D, et al . Lamin A and ZMPSTE 24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 2004;13:2493-503.  Back to cited text no. 8
    
9.
Navarro CL, Esteves-Vieira V, Courrier S, Boyer A, Duong Nguyen T, Huong le TT, et al . New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update. Eur J Hum Genet 2014;22:1002-11.  Back to cited text no. 9
    
10.
Matuleviciene A, Meskiene R, Morkuniene A, Ambrozaityte L, Meskauskas R, Garunkstiene R, et al . Frame shift mutations of the ZMPSTE24 gene in two siblings with restrictive dermopathy. Clin Dysmorphol 2016;25:7-11.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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