Clinical characterization of the HB cohort
The clinical features of the 30 patients who developed HB are described
in Table 1 ; the details of their tumors can be found inSupplementary Table 1 . The mean age at HB diagnosis was 24
months, excluding one patient who was diagnosed at 17 years (P07).
Twenty-one patients were male (70%), which is in agreement with the
literature on sex bias in HB [14, 42]. Six patients
(~20%) presented with a family history of cancer
(relatives of different degrees developed different tumors at varying
ages).
Fifteen patients were diagnosed with high-risk HB, classified according
to the CHIC stratification [43, 44], and 10 presented pulmonary
metastasis at diagnosis. Except for P23, who underwent surgery at
diagnosis, all patients received neoadjuvant chemotherapy protocols
followed by tumor resection or transplantation. Seven patients received
a liver transplant, and two relapsed. Four patients died from the
disease.
Six out of the 30 patients were born prematurely (<37 weeks),
corresponding to 20% of the group. Eleven patients had birth defects
(37%), and eight of them were classified as syndromic due to the
presentation of two or more congenital clinical features. Among them,
five patients had craniofacial anomalies, two of whom were diagnosed
with craniosynostosis (P13 and P28); two patients were born with kidney
anomalies (P11 and P09); and P07, who was diagnosed with HB at an
advanced age (17 years), was born with mild hepatomegaly.
P11, female, had a congenital HB diagnosed at one month of age; in
addition, this patient was born with unilateral renal agenesis. P13, a
male, was born extremely preterm at 27 weeks. More details about the
clinical features of both patients can be found in our previous study
[15].
Two patients were born with Hirschsprung disease and other clinical
features (P17 and P18). P17, female, was the third child of no
consanguineous parents. She was born at term, and her two siblings had a
normal phenotype. Abdominal volume and no evacuation were detected in
the first 24 hours after birth, and the diagnosis of Hirschsprung
disease was made. In the clinical evaluation at 5 years old, she
presented with global neuropsychomotor delay, facial dysmorphisms,
clinodactyly, and nail dysplasia (hypoplastic). Hepatoblastoma was
diagnosed at the age of four and classified as an epithelial subtype
with a predominance of embryonal cells, PRETEXT IV, high risk. She
underwent the SIOPEL 6 chemotherapy protocol and died before the
surgical procedure. P18, male, was the third child of a consanguineous
couple; his sister was born with congenital bilateral cataracts, while
his brother exhibited intestinal atresia-terminal ileus. The patient was
born prematurely (28 weeks), with a syndromic phenotype composed of
congenital ileal atresia, bilateral cataracts, and sensorineural
deafness. His mother, who had gestational risk (cardiac defect and
preeclampsia), died during his birth due to congestive heart failure.
Hepatoblastoma tumors were diagnosed at one year of age and classified
as fetal epithelial subtype, PRETEXT II, and low risk. He underwent a
chemotherapy protocol with cisplatin, doxorubicin, and ifosfamide,
followed by partial hepatectomy. Currently, the patient is in post
treatment follow-up, and clinical details have been previously published
[45].
P24 had facial dysmorphisms and dysplastic nails of the hands and feet,
in addition to developmental delay. P29 was born with congenital
malformations of the VACTERL spectrum and exhibited postnatal
microcephaly and developmental delay. P30 presented craniofacial
dysmorphisms, turricephaly, a short neck, laryngomalacia, a swallowing
disorder, severe bronchodysplasia, and polysyndactyly of the right
5th digit, in addition to severe malnutrition and
neuropsychomotor delay.