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Year : 2018  |  Volume : 19  |  Issue : 1  |  Page : 83-84

Hoyeraal–Hreidarsson syndrome: A rare dyskeratosis congenita phenotype

Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India

Date of Web Publication28-Dec-2017

Correspondence Address:
Mansoor C Abdulla
Department of General Medicine, M.E.S. Medical College, Perinthalmanna - 679 338, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_140_16

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How to cite this article:
Abdulla MC. Hoyeraal–Hreidarsson syndrome: A rare dyskeratosis congenita phenotype. Indian J Paediatr Dermatol 2018;19:83-4

How to cite this URL:
Abdulla MC. Hoyeraal–Hreidarsson syndrome: A rare dyskeratosis congenita phenotype. Indian J Paediatr Dermatol [serial online] 2018 [cited 2021 Dec 2];19:83-4. Available from: https://www.ijpd.in/text.asp?2018/19/1/83/206069


A 20-year-old female was referred to us with fever, vomiting, and oral ulcers. She was born out of nonconsanguineous marriage with intrauterine growth retardation (birth weight – 1.8 kg). From 6 months of age, she had recurrent episodes of fever, oral ulcers, loss of hair, finger nails, and toe nails, and generalized skin pigmentation. All developmental milestones were delayed. Her younger sibling (sister) had similar complaints, two other siblings were normal. Her weight was 27 kg (below 3rd percentile), height was 137 cm (below 3rd percentile), and had dystrophic nails, alopecia, and oral leukoplakia [Figure 1]a and [Figure 1]b. Diffuse skin pigmentation was present over anterior part of the chest, upper and lower limbs [Figure 1]c and [Figure 1]d. Intelligence was subnormal. In the hospital, she had two episodes of partial seizures. Hemoglobin was 6.0 g/dL, leukocyte count was 2500/L with 25% neutrophils, and platelet count was 10,000/mm3. Peripheral smear showed pancytopenia with macrocytosis. Biochemical parameters showed random blood sugar 131 mg%, urea 55 mg/dl, creatinine 0.7 mg/dl, sodium 120 mmol/L, potassium 3.6 mmol/L, and normal liver function test. Ultrasonography of the abdomen showed mild splenomegaly with multiple hypoechoic lesions and mild ascites. Her vasculitic workups including antinuclear antibody profile and rheumatoid arthritis were all negative. HIV, hepatitis B, and hepatitis C serologies were negative. Serum levels of folate and Vitamin B12 were normal. Bone marrow (BM) study showed hypoplastic marrow with numerous cryptococci. Computed tomography head revealed hypoplastic cerebellar vermis with prominence of superior cerebellar peduncles and widening of the 4th ventricle and interpeduncular fossa [Figure 2]. Cerebrospinal fluid (CSF) was cloudy with 28 white blood cells (lymphocytes: 96%), protein: 17 mg/dl, sugar: 48 mg/dl, and Indian ink preparation of CSF showed cryptococci. A diagnosis of Hoyeraal–Hreidarsson (HH) syndrome with cryptococcal meningitis was made since the patient had the classical triad described with dyskeratosis congenital (DKC) (dystrophic nails, skin pigmentation, and oral leukoplakia) along with intrauterine growth restriction, developmental delay, cerebellar vermis hypoplasia, and BM failure. She was managed with broad-spectrum antibiotics, antifungals, and blood component therapy, but despite all efforts, she succumbed to her illness.
Figure 1: (a and b) Clinical photograph of patient showing oral leukoplakia, (c) skin pigmentation over lower, (d) upper limbs

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Figure 2: Computed tomography head showing hypoplastic cerebellar vermis with prominence of superior cerebellar peduncles and widening of the 4th ventricle and interpeduncular fossa

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DKC is a rare genodermatosis characterized by cutaneous reticulated hyperpigmentation, nail dystrophy, premalignant leukoplakia, ulcerations affecting oral and gastrointestinal mucosa, and progressive pancytopenia.[1] HH syndrome is a rare inherited variant of DKC. This is a severe multisystem disorder mainly affecting males associated with premature mortality due to BM failure. A diagnosis of HH can be made if four of the following six most commonly recognized features are present: intrauterine growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency, or aplastic anemia.[2] The locus for the X-linked recessive form of DKC was mapped in the mid-1980s, and the dyskerin gene (DKC1) was cloned in 1998.[3] Studies over the past 10 years have demonstrated that DKC is principally a disease of defective telomere maintenance.[4],[5] The clinical symptoms and clinical course are still not clear because HH is a rare syndrome and almost all cases died before 4 years of age.[3] During literature review, it was noticed that the longest survived child was 12 years old at the time of reporting.[3] HH creates significant mortality and morbidity, with BM failure and immunodeficiency being the most serious manifestations occurring in over 80% of patients. The natural history of HH is that of death secondary to complications of BM failure or infection that usually occurs in the first decade of life. The only long-term cure for the hemopoietic abnormalities is allogeneic hematopoietic stem cell transplantation. A significant mortality is associated with BM transplants for patients with DKC when compared with other BM failure syndromes. This is an unusual case of HH since the survival is usually <5 years and this syndrome is unusual in females, and to the best of our knowledge, this is the first report of HH from the Indian subcontinent.

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  References Top

Dokal I. Inherited aplastic anaemia. Hematol J 2003;4:3-9.  Back to cited text no. 1
Walne AJ, Dokal I. Advances in the understanding of dyskeratosis congenita. Br J Haematol 2009;145:164-72.  Back to cited text no. 2
Ozdemir MA, Karakukcu M, Kose M, Kumandas S, Gumus H. The longest surviving child with Hoyeraal-Hreidarsson syndrome. Haematologica 2004;89:ECR38.  Back to cited text no. 3
Savage SA, Dokal I, Armanios M, Aubert G, Cowen EW, Domingo DL, et al. Dyskeratosis congenita: The first NIH clinical research workshop. Pediatr Blood Cancer 2009;53:520-3.  Back to cited text no. 4
Glousker G, Touzot F, Revy P, Tzfati Y, Savage SA. Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder. Br J Haematol 2015;170:457-71.  Back to cited text no. 5


  [Figure 1], [Figure 2]

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