|Year : 2022 | Volume
| Issue : 1 | Page : 80-82
An interesting case report on zinsser-engman-cole syndrome “a telomeropathy” along with ventricular septal defect
Palvi Singla, Vinita U Brahmbhatt, Kirti S Parmar, Bela J Shah
Department of Dermatology, B.J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India
|Date of Submission||01-Jun-2020|
|Date of Decision||07-Jul-2020|
|Date of Acceptance||14-Sep-2021|
|Date of Web Publication||31-Dec-2021|
Vinita U Brahmbhatt
Room No. 125, 1st Floor, OPD Building, Civil Hospital, Asarwa, Ahmedabad - 380 016, Gujarat
Source of Support: None, Conflict of Interest: None
Zinsser-Engman-Cole syndrome or dyskeratosis congenital (DKC) is a rare progressive inherited disorder which is classically defined by the triad of ectodermal dysplasia including abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. It has a highly variable phenotype and is characterized by shortening of telomeres. Here, we report a 19-year-old boy who presented to us with classic triad of DKC along with bone marrow failure and ventricular septal defect, a rare association. DKC is a rare disease but can be diagnosed by simple inspection of the mucocutaneous abnormalities.
Keywords: Bone marrow failure, dyskeratosis congenita, ventricular septal defect, Zinsser-Engman-Cole syndrome
|How to cite this article:|
Singla P, Brahmbhatt VU, Parmar KS, Shah BJ. An interesting case report on zinsser-engman-cole syndrome “a telomeropathy” along with ventricular septal defect. Indian J Paediatr Dermatol 2022;23:80-2
|How to cite this URL:|
Singla P, Brahmbhatt VU, Parmar KS, Shah BJ. An interesting case report on zinsser-engman-cole syndrome “a telomeropathy” along with ventricular septal defect. Indian J Paediatr Dermatol [serial online] 2022 [cited 2022 Jan 16];23:80-2. Available from: https://www.ijpd.in/text.asp?2022/23/1/80/334682
| Introduction|| |
Dyskeratosis congenita (DKC), a telomeropathy due to severe shortening of telomeres, is characterized by progressive bone marrow failure and the mucocutaneous triad of reticulated hyperpigmentation, nail dystrophy, and leukoplakia. Patients have an increased risk of developing myelodysplastic syndrome, acute myeloid leukemia, and gastrointestinal carcinomas. Ventricular septal defects (VSDs) and dilated cardiomyopathy can rarely be seen in DKC patients having heterozygous TINF2 mutations. Such patients have a poorer prognosis.
We here report a case of DKC in 19-year-old male who had a rare association of VSD along with classical triad of DKC.
| Case Report|| |
A 18-year-old boy patient born out of nonconsanguineous marriage presented to hospital emergency with complaints of fever, easy fatigability, and recurrent respiratory tract infections for which he was evaluated and was diagnosed with pancytopenia due to bone marrow failure. The patient was referred to skin OPD for brownish-black pigmentation over face, neck, and chest along with oral hyperpigmentation which he claimed to had since the age of 6 years and nail changes since 14 years of age. There was no family history of a similar disorder. At the age of 11 years, he was diagnosed as a case of VSD and Grade-3 aortic regurgitation. There was no history of eye complaints, loss of hair, premature graying, hyperhidrosis, dental caries, or difficulty in keeping up with studies.
On mucocutaneous examination, fine reticulate brownish-black hyperpigmentation with atrophy and telangiectasia was seen on the face, neck, upper chest giving poikilodermatous appearance [Figure 1]a which was further assessed by polarized light dermoscopy [Figure 1]b. Leukoplakia was present over bilateral buccal mucosa and tongue [Figure 2]a and [Figure 2]b. Longitudinal ridging, splitting with mild dystrophy was seen in few nails with atrophic, shiny skin over dorsa of bilateral hands [Figure 3]. No sign of any neurological deficit was there with normal sensory and motor examination.
|Figure 1: (a) Dyskeratosis congenita: Lacy, reticular pigmentation over neck and chest. (b) Dyskeratosis congenita: Polarized light dermoscopy: Pigmented lines made up of brown dots arranged in a netlike pattern (×10)|
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|Figure 2: (a and b) Dyskeratosis congenita: Leukoplakia over buccal mucosa and tongue|
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|Figure 3: Dyskeratosis congenita: Longitudinal ridging, splitting, and dystrophy over nails of the left hand|
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Informed consent was taken before taking clinical photographs.
His hemogram revealed pancytopenia with hemoglobin – 5.2, hematocrit – 31.8%, red blood cells (RBC) – 1.67 × 106/mm3, white blood cells (WBC) – 1600/mm3, platelets – 19,500/mm3 and red cell distribution width (RDW) – 17.9%, reticulocyte count – 2.63%, corrected reticulocyte count – 1.63%, and absolute reticulocyte count – 0.09 × 106/μl. Absolute neutrophil count (700/mm3) and absolute lymphocyte count (600/mm3) were decreased. Peripheral smear showed severely microcytic hypochromic anemia, moderate degree of anisopoikilocytosis, reduced RBC and WBC mass, few reactive lymphocytes, and diminished platelets. Erythrocyte sedimentation rate (85 after 1st h) and C-reactive protein (37 mg/l) were raised. Both direct and indirect Coombs test were negative. HIV, HBsAg, and HCV were nonreactive. Other relevant investigations including serum ferritin, Vitamin B12, prothrombin time, international normalized ratio, activated partial thromboplastin time, lactate dehydrogenase, liver and kidney function test were within normal limits.
Chest X-ray showed features suggestive of bronchitis and mild enlargement of cardiac size. There was no evidence of pleural or pericardial effusion. 2-D Echo (color Doppler) revealed moderate aortic regurgitation (eccentric leak), increased flow across pulmonic valve, and reduced left ventricular compliance for which he was diagnosed as a case of acyanotic small perimembranous VSD (size - 4 mm) with left to right shunt and Grade-3 aortic regurgitation. Ultrasound abdomen revealed possibility of liver parenchymal disease, splenomegaly (132 mm), dilated splenic vein (12.5 mm), and portal hypertension with dilated portal vein (14.5 mm).
Bone marrow biopsy revealed hypocellularity, micronormoblastic anemia with megaloblastic picture, dyserythropoiesis, decreased megakaryocytes, and hypolobularity with predominance of erythroid cells suggestive of bone marrow failure [Figure 4].
|Figure 4: (a and b) Bone marrow biopsy showing hypocellular marrow with decreased lobularity and predominant erythroid islands suggesting bone marrow failure (H and E; ×40 and × 100)|
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On the basis of above findings, diagnosis of DKC with bone marrow failure associated with VSD and Grade-3 aortic regurgitation was made. The relevance of reporting this case of DKC was the unusual association.
The patient was kept on a regular follow-up of 3 months to look for the progression of mucocutaneous lesions and any premalignant mucosal changes as there is increased incidence of solid malignant tumors in DKC, and these malignancies tend to develop in the mucous membranes. For bone marrow failure, he was treated successfully with an allogeneic bone marrow transplant.
| Discussion|| |
DKC is a heterogeneous congenital disorder caused by mutation in TERT, TERC, DKC1, or TINF2 genes which code for proteins that help to maintain telomeres. Zinsser (1906) was the first who described it and was then recognized as a clinical entity by Engman (1926) and Cole (1930).,,
Our patient had the classical triad of DKC with bone marrow failure which is present in 50%–90% of DKC patients and is a major cause of mortality. About 50% of cases have splenomegaly, aplastic anemia, and hypersplenism including our patient who had splenomegaly, further supporting the diagnosis.
Malignancies tend to develop during the third or fourth decade, most notably squamous cell carcinomas of the mouth, anus, cervix, vagina, esophagus, and skin. Other potential systemic manifestations include pulmonary fibrosis, liver cirrhosis, developmental delay, short stature, avascular necrosis of the femoral head, esophageal or urethral stenosis, cryptorchidism, male hypogonadism, and immunologic dysfunction leading to opportunistic infections.
Rare reported congenital heart defects include atrial and VSDs, myocardial fibrosis, and dilated cardiomyopathy, of which VSD was present in our patient. Rema et al. reported one patient with mitral regurgitation due to rheumatic heart disease which was fortuitous according to authors. This is rare association and no case reports are documented of this association in Asian continent till now.
| Conclusion|| |
We are reporting this case as it is rare to have this association. Hence, we should perform full systemic examination as it can involve any system, and frequent monitoring of patients for early detection of complications is a must. Short-term treatment for bone marrow failure includes anabolic steroids, erythropoietin, granulocyte-macrophage colony-stimulating factor. However, the only long-term curative option is allogeneic hematopoietic stem cell transplantation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]