Ataxia-telangiectasia after hepatoblastoma: The reverse chronology
- PMID: 35561060
- DOI: 10.1002/pbc.29778
To the Editor:
Hepatoblastoma is the most common liver tumour in childhood and closely linked to genetic syndromes. Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, ocular and cutaneous telangiectasia, immunodeficiency with increased sensitivity to ionizing radiation and predisposition to malignancies. Hepatoblastoma as a primary malignancy associated with AT preceding the onset of features of AT has never been reported in literature. We report a child with hepatoblastoma which occurred preceding the features of AT.
A 6-year-old female child born to second-degree consanguineous marriage, delivered at term gestation with a birth weight of 2830 g, was diagnosed with PRETEXT II standard risk hepatoblastoma at 10 months of age, when she presented with progressive abdominal distention, based on her classical radiological features. Her serum alpha feta protein (AFP) level was 25,4000 ng/ml (normal 0–10 ng/ml). Her developmental milestones were appropriate for age and she did not have any other abnormal features. As per the SIOPEL guidelines, she was treated with PLADO chemotherapy protocol and partial hepatectomy. Histology showed fetal epithelial type hepatoblastoma. At the end of treatment, the serum AFP level was 18 ng/ml.
After few months, AFP showed increasing trend ranging between 60 and 100 ng/ml. Computed Tomography (CT) of abdomen and chest done to rule out recurrence was normal. During the Covid-19 pandemic, she was lost to follow up. At 6 years of age, she reported to us with gait abnormalities in the form of swaying while walking. On examination, she had bilateral ocular telangiectasia (Figure 1). Neurological examination revealed oculomotor apraxia and pancerebellar signs suggestive of ataxia-telangiectasia. Mother also reported that the child had frequent episodes of lower respiratory tract infections since last 4 years. Clinical exome sequencing detected a homozygous missense variation in exon 50 of the ATM gene. There was no familial history of malignancy. The parents were not screened for the variants, as they were not willing for testing.
AT is caused by biallelic mutations in the ATM gene. Based on functional activity of the ATM product, mutations were classified as either loss of function (group 0) or hypomorphic mutations – missense, splice-site or deletions (group 1).1 The homozygous missense variation in exon 50 of the ATM gene that results in substitution of glutamic acid for alanine at codon 2466 has been reported in patients affected with AT. AT is associated with high incidence of cancer ranging from 10% to 20%.2 The clinical and biologic heterogeneity of AT is attributed to the type of ATM mutations and those with loss of function mutations are found to have different cancer susceptibility and survival.1 Solid tumors like hepatic B-cell non-Hodgkin lymphoma, dermatofibrosarcoma protuberans, dysgerminoma, Wilms tumor and hepatoblastoma as a second malignancy has been reported in children in AT.3, 4 AFP is found to be elevated in ataxia-telangiectasia in addition to hepatic tumors, germ cell tumors, congenital tyrosinemia and in the amniotic fluid in congenital nephrosis.5 In a population-based cohort among 160 patients with AT diagnosed between 1973 and 2020 through German Childhood Cancer Registry, they observed 19 cases of childhood cancer (15 cases of lymphoma, three cases of leukemia, and one case of medulloblastoma and no hepatoblastoma).6 Ahmed et al. have reported T-cell ALL presenting before the diagnosis of AT similar to our case.7 Suarez et al. have reported three cases (one NHL and two ALLs) in which diagnosis of AT was made 0 month, 1 month and 7 months after the diagnosis of malignancy, respectively.8
Our report highlights an association between AT and hepatoblastoma, which has not been reported previously, although our case could be a coincidence. Few studies have reported the occurrence of malignancies prior to the diagnosis of AT.