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Year : 2017  |  Volume : 18  |  Issue : 2  |  Page : 148-150

Phenotypic overlap in autosomal recessive cutis laxa: Report of two siblings

1 Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir; Department of Dermatology, STD and Leprosy, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India

Date of Web Publication27-Mar-2017

Correspondence Address:
Tasleem Arif
Al-Rahman Apartment, ground floor, Behind Zakaria market, New Sir Syed Nagar, Civil lines Aligarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.187887

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How to cite this article:
Arif T, Nisa N, Rather S, Shah S. Phenotypic overlap in autosomal recessive cutis laxa: Report of two siblings. Indian J Paediatr Dermatol 2017;18:148-50

How to cite this URL:
Arif T, Nisa N, Rather S, Shah S. Phenotypic overlap in autosomal recessive cutis laxa: Report of two siblings. Indian J Paediatr Dermatol [serial online] 2017 [cited 2020 Oct 30];18:148-50. Available from: https://www.ijpd.in/text.asp?2017/18/2/148/187887


Cutis laxa is a heterogeneous group of disorders with a wide spectrum of features. The common denominator of this condition is the presence of generalized loose skin.[1] Cutis laxa can be inherited or acquired.[1] The inherited forms include autosomal dominant, autosomal recessive, and various other syndromes where cutis laxa is associated with other extracutaneous features including Geroderma osteodysplastica, Costello's syndrome, and SCARF syndrome. The autosomal recessive type represents more severe form and is more varied, with each variant having a different defect/mutation at the protein/gene level. Three types have been described for autosomal recessive cutis laxa (ARCL) viz., ARCL-I, ARCL-II, and ARCL-III (de Barsy Syndrome).[2] Herein, we describe two siblings with ARCL-II but having some phenotypic features not usually associated with it.

  Patient-1 Top

The elder sibling, 18-year-old female (35 kg, 161 cm), whose parents were first cousins, had a progeroid appearance, downward slanting palpebral fissures, broad flat nose, sparse eyebrows, a vertically depressed frontal bone (delayed anterior fontanelle closure), hypoplastic mandible [Figure 1], lax skin over abdomen and knees, short phalanges. Additional clinical findings including follicular hyperkeratosis are listed in [Table 1]. Ophthalmological examination revealed pseudopterygium temporally in the left eye and divergent squint for which she had undergone surgery. An ultrasound of abdomen and upper gastrointestinal endoscopy revealed acalculous cholecystitis and bile gastritis. Computed tomography (noncontrast) of brain showed no lesions/abnormalities. A chest X-ray (posteroanterior view) showed normal findings while spine X-ray (anteroposterior view) showed mild scoliosis with spina bifida occulta.
Figure 1: Autosomal recessive cutis laxa in two siblings showing progeroid appearance, downward slanting palpebral fissures, broad flat nose, sparse eyebrows, a vertically depressed frontal bone (delayed anterior fontanelle closure), hypoplastic mandible

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Table 1: Clinical findings and comparison of features of patients 1 and 2

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  Patient-2 Top

Second patient, 12-year-old male (27 kg, 129.54 cm), the younger sibling, shared the similar features [Figure 1] and [Figure 2]. In addition, he also had congenital dislocation of the left hip, underdeveloped scrotal sacs with absent left testicle, limb length disproportion [Table 1]. Follicular hyperkeratosis was present on cheeks, preauricular, temporal, and submandibular areas with a background of erythema and brownish pigmentation similar to Erythromelanosis follicularis faciei et colli. The parents did not show any of the features of the disease. A skin biopsy showed features consistent with cutis laxa.
Figure 2: (a) Lax skin on the abdomen in younger sibling demonstrated by pinching the skin. (b) Note after the pinch has been released; the skin fold still persists showing the lax abdominal skin

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The inherited form of cutis laxa is uncommon with approximately 200 families reported throughout the world.[3] The approximate prevalence of ARCL is 1/120,000,000 live births.[4] ARCL-I primarily presents with pulmonary emphysema,[3] diaphragmatic defects.[5] ARCL-II (Debre type, type IIA) involves a loss of function mutation in ATP6V0A2 gene resulting in a defective N and O-Linked glycosylated serum protein. Another form of recessive cutis laxa, also known as ARCL with progeroid features (type IIB), shows a mutation in PYCR1, a mitochondrial proline metabolic enzyme.[5] Interestingly, type IIA shows phenotypic features very different from those of type IIB, by having a predilection towards neurological dysfunctions and malformations as compared to the latter which displays features such as a progeroid appearance, prognathism, hypotelorism, blue sclera, large ears, and microcephaly.[5] Similarly, other ARCL syndromes such as De Barsy Syndrome (type-III ARCL), Wrinkly Skin Syndrome, which also shows mutations in PYCR1 and Geroderma osteodysplastica share phenotypic features to an extent, with different protein/gene defects.[6]

It is quite interesting to note that this form of cutis laxa and other ARCL syndromes represent variable manifestations with some having the same genetic defect. This makes the initial diagnosis quite difficult for a clinician. The modalities available easily for detecting this condition may confirm the suspicion of the same, but the segregation and mutation screening is not always possible. There is a remarkable overlap in the phenotypic expression of this disorder in our patients with features falling into different categories of the disorder. To the best of our knowledge, this is the first report of such manifestation of ARCL from the Indian subcontinent. To summarize, the features in our patients were largely shared by type II, but a lot of other features were not inherent to it.

There is plenty of literature to support that features of ARCL type II overlap with syndromes such as Wrinkly Skin Syndrome, Geroderma osteodysplastica, and De Barsy Syndrome. The consistent findings in our patients confirm the same. Therefore, this points to the fact that one has to take into consideration the various manifestations and presentations of ARCL when encountered with a patient of the same. The clinical features are not demarcated for ARCL group of disorders. The only way one can confirm the variant is by genetic/mutation screening.[7]

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.


We are thankful to the families of our patients for their support.

Financial Support and Sponsorship


Conflicts of Interest

There are no conflicts of interest.

  References Top

Urban Z, Gao J, Pope FM, Davis EC. Autosomal dominant cutis laxa with severe lung disease: Synthesis and matrix deposition of mutant tropoelastin. J Invest Dermatol 2005;124:1193-9.  Back to cited text no. 1
Burrows NP, Lovell CR. Disorders of connective tissue. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th ed., Vol. 3. U.K: Wiley-Blackwell; 2010. p. 45.14-45.16.  Back to cited text no. 2
Morava E, Guillard M, Lefeber DJ, Wevers RA. Autosomal recessive cutis laxa syndrome revisited. Eur J Hum Genet 2009;17:1099-110.  Back to cited text no. 3
Greally MT, Kalis NN, Agab W, Ardati K, Giurgea S, Kornak U, et al. Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: Report of three affected patients. Am J Med Genet A 2014;164A: 1245-53.  Back to cited text no. 4
Berk DR, Bentley DD, Bayliss SJ, Lind A, Urban Z. Cutis laxa: A review. J Am Acad Dermatol 2012;66:842.e1-17.  Back to cited text no. 5
Scherrer DZ, Baptista MB, Matos AH, Maurer-Morelli CV, Steiner CE. Mutations in PYCR1 gene in three families with autosomal recessive cutis laxa, type 2. Eur J Med Genet 2013;56:336-9.  Back to cited text no. 6
Fischer B, Dimopoulou A, Egerer J, Gardeitchik T, Kidd A, Jost D, et al. Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. Hum Genet 2012;131:1761-73.  Back to cited text no. 7


  [Figure 1], [Figure 2]

  [Table 1]


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