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CASE REPORT
Year : 2018  |  Volume : 19  |  Issue : 4  |  Page : 360-362

Restrictive dermopathy: Report of two cases


1 Department of Dermatology, Baby Memorial Hospital, Kozhikode, Kerala, India
2 Department of Dermatology and Venereology, Government Medical College, Kozhikode, Kerala, India
3 Department of Pediatrics, Government Medical College, Kozhikode, Kerala, India

Date of Web Publication28-Sep-2018

Correspondence Address:
Dr. Sarita Sasidharanpillai
“Rohini,” Girish Nagar, Nallalom PO, Kozhikode - 673 027, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_49_17

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  Abstract 


Restrictive dermopathy is a rare entity that is fatal in the neonatal period itself. The rigidity of the skin leads to erosions, contractures, and restriction of respiratory movements. Diagnosis is often made clinically with classical features such as low-set ears, micrognathia, small, and persistently open fixed “o”-shaped mouth, translucent, shiny, rigid skin with prominent superficial blood vessels, and pseudocontractures of limb joints. We report two cases of restrictive dermopathy observed in our center within 2 years period and suggest that this condition may not be as rare as believed.

Keywords: Neonate, restrictive dermopathy, skin rigidity


How to cite this article:
Janardhanan AK, Sasidharanpillai S, Vidya AS, Francis B, Karippoth MN. Restrictive dermopathy: Report of two cases. Indian J Paediatr Dermatol 2018;19:360-2

How to cite this URL:
Janardhanan AK, Sasidharanpillai S, Vidya AS, Francis B, Karippoth MN. Restrictive dermopathy: Report of two cases. Indian J Paediatr Dermatol [serial online] 2018 [cited 2020 Feb 25];19:360-2. Available from: http://www.ijpd.in/text.asp?2018/19/4/360/242415




  Introduction Top


Restrictive dermopathy or lethal tight skin contracture syndrome is an extremely rare autosomal recessive laminopathy described by Witt et al. in 1986.[1] We report two cases of restrictive dermopathy, both of which were fatal in the 1st week of life.


  Case Reports Top


Case 1

Thirty-two weeks, preterm, small for gestational age female baby with a birth weight of 1.2 kg was referred to us. She was the first progeny of a nonconsanguineous marriage. The child was born following preterm premature rupture of membranes; the antenatal period was otherwise uneventful with a normal anomaly scan at the 20th week of gestation. At birth, the child had a weak cry and had to be resuscitated with endotracheal intubation and positive pressure ventilation with oxygen and adrenaline. APGAR score remained two both at one and at 5 min. The heart rate increased from 30/min at birth to 130/min after resuscitation. Respiratory rate was 52/min. Clinical examination revealed facial dysmorphism (hypertelorism, antimongoloid slant, low-set ears, micrognathia, small and persistently open fixed “o”-shaped mouth and pinched nose) [Figure 1], translucent, shiny, rigid skin with prominent superficial blood vessels and pseudocontractures of limb joints [Figure 2]. Vesicles and blisters appeared soon after birth, mainly on flexures and pressure areas and they ruptured to form erosions. Hair and nails were normal, and there were no prenatal teeth.
Figure 1: Child with restrictive dermopathy manifesting hypertelorism, antimangaloid slant, low-set ears, micrognathia, small and persistently open fixed “o”-shaped mouth and pinched nose)

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Figure 2: Translucent shiny rigid skin with prominent superficial blood vessels and pseudocontractures of limb joints in restrictive dermopathy

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Case 2

Two years later, we saw another preterm small for gestational age female baby (delivered at 31 weeks of gestation with birth weight 1.1 kg) who was also delivered following preterm premature rupture of membrane. The child was the first born of her parents. There was no history of consanguinity. The antenatal period was uneventful with a normal anomaly scan at 20 weeks. APGAR at birth and after 5 min was 3. The baby was resuscitated and intubated.

The child had clinical features which were an exact replica of the first case [Figure 3].
Figure 3: Child with restrictive dermopathy showing the typical facies, prominent superficial blood vessels and flexion contractures

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Skin biopsy could not be performed in both cases since parents refused to give consent. The planned skeletal survey and molecular diagnosis could not be carried out since babies expired on the 2nd and 3rd day of life, respectively, and since parents refused an autopsy.

The typical clinical presentation and the fatal course in the early days of life pointed to the diagnosis of restrictive dermopathy in both cases.[2]


  Discussion Top


In restrictive dermopathy, the rigidity of skin leads to secondarily generalized flexion contractures and restriction of respiratory movements resulting in early death.[1] In addition to the clinical features observed in our cases, other manifestations reported include rocker bottom feet and prenatal teeth.[1]

Heterozygous mutations documented in ZMPSTE24 gene, its recurrence in families and its association with consanguinity support a simple autosomal recessive mode of inheritance for restrictive dermopathy.[3],[4] ZMPSTE24 codes for a zinc metalloproteinase that plays a role in lamin A maturation. In restrictive dermopathy, accumulation of farnesyl-prelamin A occurs at the nuclear membrane. The recent identification of a single inactivating heterozygous mutation in ZMPSTE24 in unrelated, nonconsanguineous families suggests a digenic mode of inheritance also.[5]

Restrictive dermopathy is caused by a primary defect in synthesis and orientation of collagen and a significant reduction in elastic tissue. The same mechanism in fetal membranes causes amniotic fragility. The reduced strength of chorion and the lack of its normal support are postulated to precipitate chorion amnion separation that results in premature rupture of membranes as observed in our cases.[6]

Diagnosing restrictive dermopathy is rather straightforward with the typical clinical features. Characteristic histology features described in skin biopsy are thin dermis, flattening of rete ridges, the paucity of skin appendages, abnormal dense collagen bundles that run parallel to the epidermis, and near total absence of elastic fibers.[2] Dermal patches of dense collagen, fibroblasts with abundant endoplasmic reticulum and unusually, small tonofilaments are the reported electron microscopy findings.[7] Genetic analysis to detect ZMPSTE24 mutation and radiological investigations for skeletal changes such as enlarged fontanelles, clavicular dysplasia, and reduced bone density may help in doubtful cases.[1],[2],[3],[4]

The differential diagnoses considered in our cases were Pena-Shokeir phenotype, cerebro-oculo-facio-skeletal syndrome, lethal multiple pterygium syndrome, and Neu Laxova syndrome. Predominant features of Pena Shokier phenotype are multiple ankylosis, pulmonary hypoplasia and facial dysmorphism. In cerebro-oculo-facio-skeletal syndrome deformities of the eye and spine predominates. The features that favored a diagnosis of restrictive dermopathy in our patients were persistently open fixed “o”-shaped mouth, translucent, shiny, rigid skin with prominent superficial blood vessels and flexural erosions. In addition, our cases lacked the multiple pterygium of lethal multiple pterygium syndrome and characteristic edema and ichthyosis of Neu Laxova syndrome.[7],[8],[9]

Diagnosing the condition is important to define prognosis, for genetic counseling and for prenatal diagnosis. Clue to prenatal diagnosis lies in decreased fetal movement and joint contractures detected in high-resolution or three-dimensional ultrasound scanning after 16 weeks, but these are rather nonspecific so that it is difficult to decide on therapeutic abortions.[1],[2] Chorionic villous sampling at 22–24 weeks of gestation help in prenatal diagnosis.[2] This was not performed in either of our patients in the absence of similar history in any of the family members.

No therapeutic options are available to date, and it is recommended to avoid unnecessary interventions considering the certain fatal course of the disease in the neonatal period itself. Secondary infections and respiratory insufficiency are the major causes of death and mostly occur within the 1st week of life.[2]

Around eighty cases of restrictive dermopathy are reported worldwide.[10] The study observation of two cases of restrictive dermopathy in 2 years from the same center suggests that the attributed rarity of the condition could be partly due to nondiagnosis caused by the medical unfamiliarity with this entity.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Witt DR, Hayden MR, Holbrook KA, Dale BA, Baldwin VJ, Taylor GP, et al. Restrictive dermopathy: A newly recognized autosomal recessive skin dysplasia. Am J Med Genet 1986;24:631-48.  Back to cited text no. 1
    
2.
Lu CS, Wu SC, Hou JW, Chu CP, Tseng LL, Lue HC, et al. Restrictive dermopathy: Report of two siblings. Pediatr Neonatol 2013;54:198-201.  Back to cited text no. 2
    
3.
Mok Q, Curley R, Tolmie JL, Marsden RA, Patton MA, Davies EG, et al. Restrictive dermopathy: A report of three cases. J Med Genet 1990;27:315-9.  Back to cited text no. 3
    
4.
Moulson CL, Go G, Gardner JM, van der Wal AC, Smitt JH, van Hagen JM, et al. Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J Invest Dermatol 2005;125:913-9.  Back to cited text no. 4
    
5.
Barrowman J, Wiley PA, Hudon-Miller SE, Hrycyna CA, Michaelis S. Human ZMPSTE24 disease mutations: Residual proteolytic activity correlates with disease severity. Hum Mol Genet 2012;21:4084-93.  Back to cited text no. 5
    
6.
Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Geneviève 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.  Back to cited text no. 6
    
7.
Kim YN, Jeong DH, Jeong SJ, Sung MS, Kang MS, Kim KT, et al. Complete chorioamniotic membrane separation with fetal restrictive dermopathy in two consecutive pregnancies. Prenat Diagn 2007;27:352-5.  Back to cited text no. 7
    
8.
Paladini D, Tartaglione A, Agangi A, Foglia S, Martinelli P, Nappi C, et al. Pena-shokeir phenotype with variable onset in three consecutive pregnancies. Ultrasound Obstet Gynecol 2001;17:163-5.  Back to cited text no. 8
    
9.
Lazjuk GI, Lurie IW, Ostrowskaja TI, Cherstvoy ED, Kirillova IA, Nedzved MK, et al. Brief clinical observations: The Neu-Laxova syndrome – A distinct entity. Am J Med Genet 1979;3:261-7.  Back to cited text no. 9
    
10.
Available from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php.” with “http://www.orpha.net/consor/cgi-bin/OC_Exp.php. [Last accessed on 2015 Feb 18].  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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