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Table of Contents 
CASE REPORT
Year : 2016  |  Volume : 61  |  Issue : 1  |  Page : 81-84
A 5-year journey with cutis laxa in an Indian child: The de barsy syndrome revisited


1 Department of Pediatric Medicine, North Bengal Medical College, Siliguri, West Bengal, India
2 Department of Dermatology, Venereology, and Leprosy, R. G. Kar Medical College, Kolkata, West Bengal, India
3 Department of Pediatric Medicine, R. G. Kar Medical College, Kolkata, West Bengal, India

Date of Web Publication15-Jan-2016

Correspondence Address:
Abhijit Dutta
Department of Pediatric Medicine, North Bengal Medical College, Siliguri, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.174031

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   Abstract 

De Barsy syndrome (DBS), synonymously known as autosomal recessive cutis laxa type III, is an extremely rare condition clinically characterized by cutis laxa, a progeroid appearance, and ophthalmologic abnormalities. We present here an account of 5-year follow-up since the birth of an Indian boy with DBS, who had a few rare and unusual manifestations. In addition, our case probably represents the first reported case of DBS from India.


Keywords: Cutis laxa, De Barsy syndrome, progeria


How to cite this article:
Dutta A, Ghosh SK, Ghosh A, Roy S. A 5-year journey with cutis laxa in an Indian child: The de barsy syndrome revisited. Indian J Dermatol 2016;61:81-4

How to cite this URL:
Dutta A, Ghosh SK, Ghosh A, Roy S. A 5-year journey with cutis laxa in an Indian child: The de barsy syndrome revisited. Indian J Dermatol [serial online] 2016 [cited 2020 Nov 26];61:81-4. Available from: https://www.e-ijd.org/text.asp?2016/61/1/81/174031

What was known?

  • The De Barsy syndrome is an exceedingly rare autosomal recessive disorder characterized by cutis laxa, progeroid look, and corneal clouding.



   Introduction Top


The De Barsy syndrome (DBS) is an extremely rare autosomal recessive disorder characterized by cutis laxa, progeroid look, and corneal clouding. [1] After the initial description by De Barsy et al. in 1968, only a few cases have been reported in the English-language literature till date. [1],[2],[3] The disorder was recognized as a subgroup of the cutis laxa syndrome (cutis laxa type III) and expressed in variable presentations involving ocular, skeletal, dermatologic, and neurologic abnormalities. [1] We describe here, the evolution of a child with DBS with a few rare and unusual manifestations. We present here an account of a 5-year follow-up of this boy since birth. Furthermore, our case probably represents the first reported case of DBS from India.


   Case Report Top


A newborn Muslim boy from Eastern India, born out of consanguineous parentage, was admitted to the neonatal care unit of our hospital. His mother had a normal pregnancy. However, her late antenatal ultrasonography (USG) showed features of marked intrauterine growth retardation (IUGR). Following normal delivery, the baby needed no active resuscitation and the immediate postnatal period was uneventful. His other three siblings and first-degree relatives were normal. On examination, the boy showed asymmetrical IUGR. His weight, length, and head circumference were 1.85 kg (0.65 kg below the 3 rd percentile), 43.2 cm (3.1 cm below the 3 rd percentile) and 32.8 cm (0.7 cm above 3 rd percentile), respectively.

We noted that he had distinctive dysmorphic features [Figure 1] including small face with progeroid look, asymmetrical head with widely open fontanelles, thin sparse scalp hair, small nose with long philtrum, large and low set ear, and small mouth. Hypertrichosis was evident over the forehead. He had thin translucent lax skin with prominent superficial blood vessels. The nails were normal. Examination of the musculoskeletal system showed flexion deformity of both wrist joints with claw-like fingers and subluxation of multiple small joints. In the lower limbs talipes with equinus deformity was present. The baby was hypotonic. He also had large bilateral inguinal hernia [Figure 2]. Other systemic examinations did not reveal any abnormality. Complete hemogram and biochemical panels including thyroid, hepatic, and renal functions were normal. USG of the abdomen, echocardiography, and skeletal X-ray did not reveal any abnormality. His karyotype was normal.
Figure 1: (a) Progeroid look, asymmetrical head, and thin sparse scalp hair, small nose with long philtrum, large and low set ear, small mouth, and hypertrichosis over the forehead. (b) Thin translucent lax skin with prominent superficial blood vessels and flexion deformity of both wrist joints with claw-like fingers

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Figure 2: (a) Bilateral an inguinal hernia (b) X-ray showing multiple loops of dilated intestine suggestive of an inguinal hernia

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At the age of 2 months, the progeroid look and corneal opacity became more apparent, and strabismus was evident. The inguinal hernia also became more prominent, and he developed torticolis.

During follow-up, delayed developmental milestones were noted. Social smile developed at 4 months of age, neck holding at 6 months, sitting without support at 18 months, and walking at 2.5 years. He developed generalized tonic-clonic convulsion at the age of 3.5 years. Electroencephalography (EEG) at that time showed features of generalized seizure disorder and he was put on the antiepileptic drug. Computerized tomography scan of the brain (done twice) showed normal brain parenchyma, except features of dysraphism of the splenium of the corpus callosum and a mild degree of colpocephaly [Figure 3]. Magnetic Resonance Imaging of the brain was attempted, but could not be done due to repeated failure to sedate the child. At the time of last follow-up, he was 5-year-old. He could walk with an unsteady gait.
Figure 3: Axial (a) and sagittal (b) section of plain computerized tomography scan of brain showing mild degree of colpocephaly of right lateral ventricle and dysraphism of splenium of corpus callosum

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His weight was10 kg (4.3 kg below the 3 rd percentile), height was 93 cm (8.2 cm below the 3 rd percentile). He had a progeroid and grimacing face, convergent squint, asymmetrical head with frontal bossing, and torticolis. His head circumference is 46.5 cm (1.4 cm below the 3 rd percentile). Neurologically, he had generalized hypotonia, athetoid movements of limbs, and brisk tendon jerks. He has moderate mental retardation. He is socially adjusted, plays with friends, and can utter a few meaningful words. We needed to accelerate the dose of the antiepileptic drug for his recurrence of convulsion.

Dermatological evaluation at that time revealed thin, atrophic, wrinkled skin especially over his dorsum of the hands and feet with reduced subcutaneous fat. Teeth and nails were well-developed. Small joints were hyperextensible. Movements of the large joints were normal. Inguinal hernia had been successfully operated and torticolis was partially corrected [Figure 4]. Skin biopsy, done twice on the 3 rd day after birth and at the age of 4.5 years, showed hyperkeratosis, but an otherwise normal epidermis, fragmented collagen in the dermis with preservation of adnexae. Verhoeff van Gieson stain showed markedly reduced elastic tissue fibers in the mid and lower dermis and presence of small fragmented elastic fibers [Figure 5]. Based on the clinical features and histological findings, a diagnosis of DBS was made.
Figure 4: (a) Progeroid skin, (b) hyperextensibility of joints (c) thin skin with mild vascular prominence, (d) scars after operation of an inguinal hernia, (e) present appearance

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Figure 5: Histopathology showing hyperkeratosis but an otherwise normal epidermis, fragmented collagen in the dermis with preservation of adnexae (a) (H and E, ×40), (b) (H and E, ×100), and (c) (H and E, ×400), Verhoeff van Gieson stain showed markedly reduced elastic tissue fibers in the mid and lower dermis and presence of small fragmented elastic fibers ((d): ×40, (e): ×100, (f): ×400)

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   Discussion Top


Since the initial description of DBS, only a few cases have been described in the literature with diverse phenotypic features. The exact pathogenesis of DBS remains elusive.

Elastic fiber abnormality in the form of sparse, small, fragmented fibers in the dermis with small fibers per unit area is probably the main underlying cause of this disorder. Molecular hybridization studies demonstrated reduced elastin mRNA steady-state levels as compared with age-matched control individuals. The progeroid appearance originates due to hypoplasia of the dermis. [3],[4],[5]

There is no racial variation, but male predominance has been noted. [2] History of the reported cases may suggest an autosomal recessive mode of inheritance and affection of other siblings in the same family has been noted. [4],[6] They have dysmorphic features such as the progeroid look, prominent forehead; large low set dysplastic ears, sparse hair, small mouth with thin lips, and small upturned nose. The majority (96%) of the affected children have IUGR and show postnatal growth retardation. [2]

Besides cutis laxa, thin translucent skin with reduced subcutaneous fat has been described, and inguinal and umbilical hernia has been noted in 34% cases. [2],[7]

Congenital corneal opacity due to degeneration of Bowman's membrane was seen in 48% of cases and cataract, myopia, strabismus, and blue sclera has been seen in varying proportion. [8]

Developmental delay since birth has been seen in 76% of cases while 48% showed severe delay. Hypotonia, athetoid movement, grimacing, and seizures have also been reported. [2],[6],[7] Hyper extensible joints with subluxation or dislocation of small joints, sclerosis, pectus excavatum, congenital vertical talus and hip dysplasia or dislocation have all been described. [9],[10]

Although nonspecific EEG changes and ventricular dilatation have been described in the literature, dysraphism of the splenium of corpus callosum with a mild degree of colpocephaly was a unique feature in our patient. The lifespan of the patients with this syndrome is unknown. To the best of our knowledge, the oldest reported case was of a 24-year-old at the time of reporting. [6]

Other progeroid conditions are the close differential diagnoses of DBS. However, distinctive morphological features along with skin biopsy will help distinguishing others. Mutation in PYCR1, coding for a mitochondrial enzyme involved in proline metabolism may have a causative role in DBS. [11] However, the genetic study could not be performed in the present case because of local unavailability and financial constraints. Based on the specific mutation patterns, DBS may also be divided into an autosomal recessive cutis laxa type IIIA (due to mutations in ALDH18A1) and autosomal recessive cutis laxa type IIIB (due to mutations in PYCR1). [12],[13] Till date, less than 30 cases of DBS have been reported in the PubMed, Medline, and PubMed Central databases. We have searched these databases, Google Scholar, and standard textbooks with the terms such as, "De Barsy," India, and "Indian." However, in spite of our best effort, we could not find any report in Indian population. As there is no specific therapy for this condition, we seek to emphasize the importance of regular follow-up in order to address the different evolving problems in these patients.

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.
Toriello HV. Premature ageing syndromes. In: Irvine AD, Hoeger PH, Yan AC, editors. Text Book of Pediatric Dermatology. 3 rd ed. Oxford: Willey-Blackwell; 2011. p. 134.1-134.19.  Back to cited text no. 1
    
2.
Kivuva EC, Parker MJ, Cohen MC, Wagner BE, Sobey G. De Barsy syndrome: A review of the phenotype. Clin Dysmorphol 2008;17:99-107.  Back to cited text no. 2
    
3.
Guerra D, Fornieri C, Bacchelli B, Lugli L, Torelli P, Balli F, et al. The De Barsy syndrome. J Cutan Pathol 2004;31:616-24.  Back to cited text no. 3
    
4.
Pontz BF, Zepp F, Stöss H. Biochemical, morphological and immunological findings in a patient with a cutis laxa-associated inborn disorder (De Barsy syndrome). Eur J Pediatr 1986;145:428-34.  Back to cited text no. 4
    
5.
Karnes PS, Shamban AT, Olsen DR, Fazio MJ, Falk RE. De Barsy syndrome: Report of a case, literature review, and elastin gene expression studies of the skin. Am J Med Genet 1992;42:29-34.  Back to cited text no. 5
    
6.
Kunze J, Majewski F, Montgomery P, Hockey A, Karkut I, Riebel T. De Barsy syndrome - An autosomal recessive, progeroid syndrome. Eur J Pediatr 1985;144:348-54.  Back to cited text no. 6
[PUBMED]    
7.
Cheriathu J, D'souza IE, John LJ, Bahtimi RE. Progeroid syndrome of De Barsy with hypocalcemic seizures. J Nepal Paediatr Soc 2012;32:175-7.  Back to cited text no. 7
    
8.
Aldave AJ, Eagle RC Jr, Streeten BW, Qi J, Raber IM. Congenital corneal opacification in De Barsy syndrome. Arch Ophthalmol 2001;119:285-8.  Back to cited text no. 8
    
9.
Stanton RP, Rao N, Scott CI Jr. Orthopaedic manifestations in De Barsy syndrome. J Pediatr Orthop 1994;14:60-2.  Back to cited text no. 9
    
10.
Arazi M, Kapicioglu MI, Mutlu M. The De Barsy syndrome. Turk J Pediatr 2001;43:79-84.  Back to cited text no. 10
    
11.
Leao-Teles E, Quelhas D, Vilarinho L, Jaeken J. De Barsy syndrome and ATP6V0A2-CDG. Eur J Hum Genet 2010;18:526.  Back to cited text no. 11
[PUBMED]    
12.
#614438-CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIB; ARCL3BCytogenetic Locations: 17q25.3 OMIM: 614438. Available from: http://www. omim.org/entry/614438 . [Last accessed on 2015 Aug 11].  Back to cited text no. 12
    
13.
#219150-CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A.Cytogenetic Locations: 10q24.1.OMIM: 219150. Available from: http://www.omim.org/entry/219150. [Last accessed on 2015 Aug 11]  Back to cited text no. 13
    

What is new?

  • The present case probably represents the first reported case of De Barsy syndrome (DBS) from India
  • This patient of DBS had a few rare and unusual manifestations.


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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