Abstract

Williams?Beuren syndrome (WBS) is a rare neurodevelopmental genetic disorder associated with microdeletion at the long arm of chromosome 7 (7q11.23). Few cases have been reported with WBS with hemato oncological malignancies. Herein, we report Burkitt leukemia in a 5 year old girl with WBS. We like to call attention to the management of this rare combination.

Introduction

Williams syndrome is a rare neurodevelopmental disorder, also known as Williams?Beuren syndrome (WBS). WBS is a sporadic genetic disorder that occurs in 1:20000?1:50000. The characteristic features of WBS include dysmorphic face, cardiovascular disease (especially aortic stenosis), mental retardation, hypercalcemia, growth deficiency, high sociability, and friendly personality. Furthermore, children with WBS have characteristic craniofacial features such as periorbital fullness, medial eyebrow flare, stellate iris, flat nasal bridge, strabismus, long philtrum, wide mouth, full cheeks, and lips.[1] [2]

Patients with WBS have microdeletion of 25?30 genes in q11.23 regions of chromosome 7. WBS is not considered as a cancer predisposition syndrome.[3] In the medical literature review, single reports of astrocytoma, ovarian mucinous cystadenoma, follicular thyroid carcinoma, Wilms tumor, non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL) in association with WBS have been published.[4] [5] [6]

Herein, we report on the clinical course and laboratory findings of a patient with WBS who also had Burkitt leukemia.

Case Report

At initial presentation, the patient, a 5-year-old girl with WBS, was referred to our hospital for evaluation of abdominal mass. In her medical history, mother and father were not relatives. She was diagnosed with WBS when she was 4 months old. Aortic valve replacement operation was performed due to supravalvular aortic stenosis when she was 15 months old. She had initial complaints of abdominal swelling, constipation, and fatigue for 4 days. On physical examination at the time of admission, body weight was 15 kg (10?25p), height was 104 cm (25p), and general state was good, and there was no petechiae and purpura. Vital signs were in normal range. The patient showed many of the features such as elfin face, mild mental retardation, swollen eyelids, high palate, epicanthal folds, periorbital fullness, full lower lips, and small mandible. She was also talkative, social, and friendly. There were 10 cm scar over the sternum because of cardiovascular surgery, second-degree murmur, suspected mass in deep palpitation, and no hepatosplenomegaly. Urine analysis was normal. The patient?s white blood cell count was 9770/mm3, hemoglobin level was 11 gr/dL, and platelet count was 522000/mm3. Peripheral blood smear showed atypical vacuolated lymphoblasts. The patient had elevated lactate dehydrogenase (2561 IU/L), aspartate aminotransferase (203 U/L), and alanine aminotransferase (58 U/L). Serum uric acid, albumin, creatinine, and blood urea nitrogen levels were in normal range. Abdominal ultrasound, computed tomography scan, and magnetic resonance images revealed multiple parenchymal nodular mass lesions in the liver and kidneys; abdominal mass lesion in the subhepatic area; para-aortic and mesenteric lymphadenomegaly; and diffuse wall thickening involving terminal ileum, cecum, and ascending colonic segments suggesting of lymphomatous involvement.

Bone marrow aspiration revealed 60% of blasts with many vacuoles and L3 morphology. Immunophenotypical analyses showed that blast expressed CD 10, CD19, CD 20, HLA-DR, and cytoplasmic IgM but were negative for CD14, MPO, CD33, CD13, surface IgM, CD2, CD7, CD11, Glycophorin A, cytoplasmic Tdt, and cytoplasmic CD3. The patient was diagnosed with Burkitt leukemia. The patient was treated as standard risk group ALL with national Turkish BFM protocol.[7] Cytogenetic analyses showed 46, XX.

Abdominal distension resolved after steroid treatment. Chemotherapy course was complicated by sepsis and fungal infection. She was treated with antimicrobial and antifungal drugs. The response of chemotherapy was perfect. She has under outpatient control without any complications, and there is no recurrence for a follow-up period of 7.5 years.

Discussion

Although WBS is not considered a clear cancer predisposing syndrome, the numbers of published cases of malignancies associated with WBS in pediatric adult group have been increasing. The types of malignancies are limited. The most common malignancies are lymphoma and leukemia groups (especially mature B cell originated). In the childhood group, Burkitt lymphoma in six cases, B cell lymphoblastic lymphoma in one, T cell lymphoblastic lymphoma in one, and ALL in one have been reported. In addition to hematological malignancies, two cases of astrocytomas, one case of mucinous cystadenoma of ovary, one case of Wilms tumor, and one case of follicular thyroid carcinoma have been reported in childhood [Table 1].[1] [2] [4] [5] [6] [8] [9] Culic?et al.[8] reported a 14-year-old boy with WS and hyperploidic ALL; in this report, the immunological origin of the patient was not given; our presented case is the youngest children with mature B cell leukemia lineage.

1. Zhukova N, Naqvi A.?Williams-beuren syndrome and burkitt leukemia. J Pediatr Hematol Oncol 2013; 35: e30-2
2. Vanhapiha N, Knuutila S, Vettenranta K, Lohi O.?Burkitt lymphoma and ewing sarcoma in a child with williams syndrome. Pediatr Blood Cancer 2014; 61: 1877-9
3. Decimi V, Fazio G, Dell?Acqua F, Maitz S, Galbiati M, Rizzari C. et al.?Williams syndrome and mature B-leukemia: A random association?. Eur J Med Genet 2016; 59: 634-40
4. Chagas NB, Maion VH, de Av? LR, Matheucci J?nior E, Moutinho MA, Melo DG. et al.?Follicular thyroid carcinoma in a male adolescent with williams-beuren syndrome. Clin Dysmorphol 2017; 26: 44-6
5. Chonan M, Kanamori M, Kumabe T, Saito R, Watanabe M, Tominaga T. et al.?Pilomyxoid astrocytoma of the cerebellum with williams syndrome: A case report. Childs Nerv Syst 2013; 29: 1211-4
6. Marles SL, Goldberg NA, Chudley AE.?Mucinous cystadenoma of ovary in a patient with williams syndrome. Am J Med Genet 1993; 46: 349
7. Yuksel Soycan L.?BFM-TR ALL 2000:First Turkish multicentric study in the treatment of pediatric acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2007; 29: 21
8. Culic V, Culic S, Armanda V, Resic B, Lasan R, Peterlin B. et al.?Single signal of the williams syndrome chromosome region 1 gene in hyperploidic bone marrow cells of acute lymphoblastic leukemia in a williams syndrome patient. Med Pediatr Oncol 2002; 38: 205-7
9. Guenat D, Merla G, Deconinck E, Borg C, Rohrlich PS.?DNA damage response defect in williams-beuren syndrome. Int J Mol Med 2017; 39: 622-8
10. Hasle H, Olsen JH, Hansen J, Friedrich U, Tommerup N.?Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities. Cancer Genet Cytogenet 1998; 105: 39-42
11. Guenat D, Quentin S, Rizzari C, Lundin C, Coliva T, Edery P. et al.?Constitutional and somatic deletions of the williams-beuren syndrome critical region in non-hodgkin lymphoma. J Hematol Oncol 2014; 7: 82

Address for correspondence

Publication History

Article published online:
24 May 2021

? 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

1. Zhukova N, Naqvi A.?Williams-beuren syndrome and burkitt leukemia. J Pediatr Hematol Oncol 2013; 35: e30-2
2. Vanhapiha N, Knuutila S, Vettenranta K, Lohi O.?Burkitt lymphoma and ewing sarcoma in a child with williams syndrome. Pediatr Blood Cancer 2014; 61: 1877-9
3. Decimi V, Fazio G, Dell?Acqua F, Maitz S, Galbiati M, Rizzari C. et al.?Williams syndrome and mature B-leukemia: A random association?. Eur J Med Genet 2016; 59: 634-40
4. Chagas NB, Maion VH, de Av? LR, Matheucci J?nior E, Moutinho MA, Melo DG. et al.?Follicular thyroid carcinoma in a male adolescent with williams-beuren syndrome. Clin Dysmorphol 2017; 26: 44-6
5. Chonan M, Kanamori M, Kumabe T, Saito R, Watanabe M, Tominaga T. et al.?Pilomyxoid astrocytoma of the cerebellum with williams syndrome: A case report. Childs Nerv Syst 2013; 29: 1211-4
6. Marles SL, Goldberg NA, Chudley AE.?Mucinous cystadenoma of ovary in a patient with williams syndrome. Am J Med Genet 1993; 46: 349
7. Yuksel Soycan L.?BFM-TR ALL 2000:First Turkish multicentric study in the treatment of pediatric acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2007; 29: 21
8. Culic V, Culic S, Armanda V, Resic B, Lasan R, Peterlin B. et al.?Single signal of the williams syndrome chromosome region 1 gene in hyperploidic bone marrow cells of acute lymphoblastic leukemia in a williams syndrome patient. Med Pediatr Oncol 2002; 38: 205-7
9. Guenat D, Merla G, Deconinck E, Borg C, Rohrlich PS.?DNA damage response defect in williams-beuren syndrome. Int J Mol Med 2017; 39: 622-8
10. Hasle H, Olsen JH, Hansen J, Friedrich U, Tommerup N.?Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities. Cancer Genet Cytogenet 1998; 105: 39-42
11. Guenat D, Quentin S, Rizzari C, Lundin C, Coliva T, Edery P. et al.?Constitutional and somatic deletions of the williams-beuren syndrome critical region in non-hodgkin lymphoma. J Hematol Oncol 2014; 7: 82