Keywords
Burkitt leukemia - child - Williams–Beuren syndrome
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.
Table 1
Literature review of hemato-oncological malignancies in children with Williams-Beuren
syndrome
|
Author (year)
|
Age at diagnosis (year)
|
Malignancies
|
|
NHL – Non-Hodgkin lymphoma; ? – Unknown gender
|
|
Semmekrot et al., 1985-1986
|
5, ?
|
Astrocytoma
|
|
Marles et al., 1993
|
?, female
|
Mucinous cystadenoma of ovary
|
|
Felice et al., 1994
|
29, female
|
NHL
|
|
Culic et al., 2002
|
14, male
|
Acute lymphoblastic leukemia
|
|
Amenta et al., 2004
|
8, male
|
NHL (Burkitt)
|
|
Thornburg et al., 2005
|
5, female
|
NHL (Burkitt)
|
|
Togo et al., 2007
|
5, female
|
Cutaneous fibrous hamartoma
|
|
Urisarri-Ruiz de
|
12, male
|
NHL (T-cell 9)
|
|
Cortázar et al., 2009
|
|
|
|
Onimoe et al., 2011
|
10, female
|
NHL (Burkitt)
|
|
Zhukova and Naqvi, 2013
|
8, male
|
NHL (Burkitt)
|
|
Chonan et al., 2013
|
3, male
|
Astrocytoma
|
|
Vanhapiha et al., 2014
|
9, ?
|
NHL (Burkitt) and Ewing sarcoma
|
|
Guenat et al., 2014
|
10, male
|
NHL (B-NHL)
|
|
Guenat et al., 2014
|
7, female
|
NHL (Burkitt)
|
|
Velikonja et al., 2016
|
4, ?
|
Wilms tumor
|
|
Chagas et al. 2017
|
12, male
|
Follicular thyroid carcinoma
|
|
This study, 2017
|
5, female
|
Burkitt leukemia
|
Patient with WBS have a higher risk of mortality in normal life compared to normal
healthy population. During the treatment of WBS with malignancies have higher risk
of morbidity and mortality because of anesthesia, surgery, sedation, and chemotherapy
regimen. Especially baseline cardiac examination (blood pressure, electrocardiogram,
and echocardiogram) is advised during the pre- and post-treatment period. On the another
hand, nephrological evaluation (urinalysis, urinary ultrasound, and Doppler examination)
is recommended before the treatment.[1] Our patients did not experience any cardiac problem like arrhythmia. On the other
hand, she had hyperglycemia related to chemotherapy protocol including steroid and
asparaginase.
Chromosome 7 is the most common involved chromosome among the cytogenetic aberrations
in the malignancies. Especially, monosomy 7 is a famous genetic predisposition to
myelodysplastic syndrome and secondary acute myeloid leukemia. Hasle et al.[10] reported the relationship between chromosome 7 and epithelial, hematologic malignancies
from the database of Danish cytogenetic registry. They found that five persons with
constitutive chromosome 7 abnormality associated cancer including one thyroid carcinoma,
three carcinomas of the digestive tract, and one malignant melanoma. There was no
identified cancer in the patients with WBS in this study.
There are no large clinic, molecular genetic correlation studies of gen deletions
of WBS and development of cancer mechanism. Among the 20 genes that are mapped in
affected religion of chromosome 7q11.23, four of these genes are speculated to be
responsible for different clinical features of WBS: (1) the elastin gene was found to associated with the phenotypical features of WBS such as cardiac
features, (2) LIM-kinase 1 gene abnormalities had been implicated with visual and cognition problems, (3)
DNA repair genes such as BAZ1B, RFC2, and GTF2I are related with cancer development, (4) BCL7A, BCL7B genes which regulates the apoptosis, has been found to be closely related with B
cell leukemia and lymphoma.[1]
[3]
[9]
[11] Although the fluorescence in situ hybridization aberration of our presented case has been performed, the molecular
genetic studies were not done.
Conclusion
Currently, it is not possible to explain the correlation between hemato-oncological
malignancies and genetic variation of WBS. It is important to report these cases to
literature to call attention to this syndrome for the clinicians.
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.
