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CASE REPORT
Year : 2021  |  Volume : 22  |  Issue : 4  |  Page : 370-373

Kin with no skin: Johanson–Blizzard syndrome in siblings: A rare association of aplasia cutis congenita


Department of Dermatology and Venereology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission04-Dec-2020
Date of Decision21-Jun-2021
Date of Acceptance27-Jun-2021
Date of Web Publication01-Oct-2021

Correspondence Address:
K Kavya Shree
Room No. 110, BMC Ladies Hostel, Opposite Tipu Sulthan Summer Palace, Chamrajpet, Bengaluru - 560 002, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.ijpd_172_20

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  Abstract 


Johanson–Blizzard syndrome (JBS) is a rare autosomal recessive disease which was first described in 1971 by Johanson and Blizzard in three unrelated girls. Less than 100 cases have been reported to date. It is characterized by exocrine pancreatic insufficiency, hypoplastic nasal alae, scalp cutis aplasia, and other features including developmental delay, failure to thrive, hearing loss, mental retardation, hypothyroidism, dental anomalies, and anomalies of the genitourinary system. The condition is caused by mutations in the UBR1 gene, which encodes the E3 ubiquitin ligase protein responsible for regulating the degradation of proteins. Aplasia cutis congenita is a rare entity characterized by localized or widespread absence of skin from birth. Scalp is the most common site to be involved. Here, we are reporting two interesting cases of JBS in siblings who had aplasia cutis as their initial cutaneous manifestation.

Keywords: Aplasia cutis congenita, Johanson–Blizzard syndrome, Exocrine pancreatic insufficiency


How to cite this article:
Asha G S, Shree K K, Revathi T N, Shilpa K. Kin with no skin: Johanson–Blizzard syndrome in siblings: A rare association of aplasia cutis congenita. Indian J Paediatr Dermatol 2021;22:370-3

How to cite this URL:
Asha G S, Shree K K, Revathi T N, Shilpa K. Kin with no skin: Johanson–Blizzard syndrome in siblings: A rare association of aplasia cutis congenita. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Nov 28];22:370-3. Available from: https://www.ijpd.in/text.asp?2021/22/4/370/327448




  Introduction Top


Johanson-Blizzard syndrome (JBS) is a very rare genetic disease which can present to dermatologists as aplasia cutis congenital (ACC) with characteristic facies. JBS belongs to group nine of Frieden's classification of ACC. This is one of the very rare causes of ACC. Here, we are reporting two cases of JBS in siblings.

The cases were examined after taking informed consent from the parents.


  Case Report Top


Case 1

A three-day-old male baby born out of consanguineous marriage was admitted to neonatal intensive care due to nonpassage of meconium and abdominal distension. This was a full-term neonate delivered by cesarean section and was appropriate for gestational age. Dermatology reference was needed in view of the localized absence of skin over the scalp. On examination, the baby had irregular ulcer (3 cm × 5 cm in maximum dimensions) over the vertex covered by hemorrhagic crust [Figure 1]. The baby had short-beaked nose and low set ears [Figure 2]. Details of ultrasound abdomen and pelvis revealed imperforate anus. Parents also gave a history of similar presentation in baby's elder brother at birth.
Figure 1: Aplasia cutis of the vertex in 3-day-old neonate

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Figure 2: Short torpedo-shaped nose and low set ears in the neonate

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Case 2

A six-year-old male child who is the sibling of the earlier case was called for examination to rule out any syndromic association. On examination, he had short-beaked nose [Figure 3], spiky hair (frontal upsweep of hair) [Figure 4], peg-shaped teeth and high arched palate [Figure 5]a and [Figure 5]b, healed scar of aplasia cutis of the scalp [Figure 6], and profound hearing loss. On further evaluation of the medical records, he had exocrine pancreatic insufficiency and hypothyroidism. This child was diagnosed as a case of JBS in the center where the colostomy was done in neonatal period. Currently, the child is on pancreatic enzyme and thyroid hormone replacements.
Figure 3: Short torpedo-shaped nose in the 6-year-old sibling of case 1

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Figure 4: Spiky hair or uprolled frontal hair

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Figure 5: (a) High arched palate, (b) Peg-shaped teeth

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Figure 6: Healed scar of aplasia cutis of scalp in the elder brother

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  Discussion Top


JBS is a very rare genetic disease with autosomal recessive inheritance. In 1971, Johanson and Blizzard described this syndrome in three unrelated girls.[1] Till date, very few cases are reported among Indians. This syndrome is caused by mutations in the UBR1 gene which encodes E3 ubiquitin ligase protein. This gene is responsible for regulating degradation of proteins.[2] JBS is characterized by exocrine pancreatic insufficiency, hypoplastic nasal alae, ACC, developmental delay, failure to thrive, hearing loss, mental retardation, hypothyroidism, conical teeth, and anomalies of genitourinary and cardiac systems. JBS is a very rare association of ACC. Peculiar torpedo-shaped nose with large nostrils, swept up hair (spiky frontal hair), and atrophic scar of ACC is seen in older children.[3] Prognosis in JBS depends on the underlying systemic involvement. Mardini et al. reported a case series of JBS, in which all three patients died in infancy from complications of malabsorption and failure to thrive.[4] If the pancreatic malabsorption problems are overcome the child can survive infancy, but it will require prolonged medical supervision.

The knowledge about ACC becomes important here to find out syndromic associations. ACC is an uncommon disorder characterized by the congenital local/widespread absence of skin. The scalp is the most common site involved, although any other sites can be involved such as trunk, thighs, palms, and soles. The estimated incidence is 1–3/10,000 births as it is slightly underreported and most of the cases go unnoticed. The typical lesion is small (up to 10 cm), well-circumscribed, noninflammatory ulcer of different shapes which may either be healed with scarring, often with a thin parchment like appearance or they can be open, with varying levels of ulceration at birth. ACC may be associated with the defects of the underlying skull if the lesion is larger than 10 cm.[5] The hair collar sign (ring of distorted hair around the lesion) is a significant indicator of underlying involvement of the dura. The location of the ACC to the vertex can be explained partially by the existence of maximum tensile force during rapid brain growth in that region.[6]

The causative factors or associations of ACC could be genetic, intrauterine trauma, intrauterine infections by varicella or herpes viruses, fetus papyraceous, various drugs such as methimazole, carbimazole, misoprostol, and valproic acid, fetofetal transfusion, and abnormal elastic fiber biomechanical forces.[7]

In 1986, Frieden classified ACC into nine groups:[8]

  • Group 1: ACC of scalp without multiple anomalies
  • Group 2: ACC of scalp with limb abnormalities
  • Group 3: ACC of scalp with epidermal and organoid nevi
  • Group 4: ACC with a hair collar overlying embryonic malformations such as meningomyelocele, omphalocele, and spinal dysraphism
  • Group 5: ACC associated with fetus papyraceous or placental infarcts
  • Group 6: ACC associated with epidermolysis bullosa
  • Group 7: ACC of the extremities without epidermolysis bullosa
  • Group 8: ACC caused by teratogen exposure, intrauterine infections, or drugs
  • Group 9: ACC associated with malformation syndromes such as  Patau syndrome More Details, JBS, Goltz syndrome, and others.


Skin biopsy is routinely not performed. It may show the absence of (or a very thin) epidermis, dermis, or deeper structures. “Loosely arranged” collagen bundles may be seen with the absence of adnexal structures and elastic fibers. Prognosis for a single superficial lesion is excellent which heals with an atrophic hairless scar over several weeks or months. Risk of mortality is high with full-thickness involvement of dura.

Management of ACC should include detailed search for any syndromic associations not mere treatment of the skin defect. There are no defined guidelines for the treatment of skin lesion. Bland ointments and topical antibiotics are applied over smaller lesions to prevent desiccation. Saline compresses may be done to remove the crust. Paraffin dressings can accelerate healing. Oral antibiotics are needed only if there are signs of infection.[9] The rule is that, in cases of large lesions, with or without deeper absence of substance, plastic surgery should be considered.[10]


  Conclusion Top


JBS is a very rare association of ACC. It should be considered as one of the causes because early supplementation of pancreatic enzymes may be lifesaving in many babies. We, the dermatologists, can play a significant role in identifying many genetic syndromes which usually present to us with the classical cutaneous features or signs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for 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.
Johanson A, Blizzard R. A syndrome of congenital aplasia of the alae nasi, deafness, hypothyroidism, dwarfism, absent permanent teeth, and malabsorption. J Pediatr 1971;79:982-7.  Back to cited text no. 1
    
2.
Zenker M, Mayerle J, Lerch MM, Tagariello A, Zerres K, Durie PR, et al. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nat Genet 2005;37:1345-50.  Back to cited text no. 2
    
3.
Hurst JA, Baraitser M. Johanson-Blizzard syndrome. J Med Genet 1989;26:45-8.  Back to cited text no. 3
    
4.
Mardini MK, Ghandour M, Sakati NA, Nyhan WL. Johanson-Blizzard syndrome in a large inbred kindred with three involved members. Clin Genet 1978;14:247-50.  Back to cited text no. 4
    
5.
İşcimen A, Yardımcı G. Aplasia cutis congenita. J Turk Acad Dermatol 2010;4:04201r.  Back to cited text no. 5
    
6.
Burkhead A, Poindexter G, Morrell DS. A case of extensive Aplasia Cutis Congenita with underlying skull defect and central nervous system malformation: discussion of large skin defects, complications, treatment and outcome. J Perinatol 2009;29:582-4.  Back to cited text no. 6
    
7.
Veronica A, Neil J, Sebire. Congenital naevi and other developmental abnormalities affecting the skin. In: Griffiths C, Barker J, Bleiker T, Chalmers R, Creamer D, editors. Rook's Textbook of Dermatology. 9th ed. United Kingdom: Wiley-Blackwell Publication; 2016. p. 1989-90.  Back to cited text no. 7
    
8.
Frieden IJ. Aplasia cutis congenita: A clinical review and proposal for classification. J Am Acad Dermatol 1986;14:646-60.  Back to cited text no. 8
    
9.
Kaur S, Sangwan A, Daval S, Dua I, Jain VK. Aplasia cutis congenital, group 5 without fetus papyraceous in two newborns. Indian J Deramatol Venereol Leprol 2016;82:695-7.  Back to cited text no. 9
    
10.
Brzezinski P, Pinteala T, Chiriac AE, Foia L, Chiriac A. Aplasia cutis congenita of the scalp--What are the steps to be followed? Case report and review of the literature. An Bras Dermatol 2015;90:100-3.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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