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Table of Contents
Year : 2022  |  Volume : 15  |  Issue : 1  |  Page : 45-47

Hepatoblastoma in an infant with cat eye syndrome

1 Department of Neonatology, Al Jalila Children's Hospital, Dubai, UAE
2 Department of Neonatology, Al Qassimi Hospital, Sharjah, UAE

Date of Submission09-Jul-2021
Date of Decision12-Aug-2021
Date of Acceptance25-Oct-2021
Date of Web Publication25-Mar-2022

Correspondence Address:
Shiva Shankar
Department of Neonatal, Al Jalila Children's Hospital, P. O. BOX: 7662, Dubai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/hmj.hmj_44_21

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Introduction: Cat eye syndrome (CES) is a rare chromosomal disorder with highly variable clinical presentations involving multiple organs. The features mimic other syndromes such as CHARGE or VACTERL, and genetic testing is required to confirm the diagnosis. CES and malignancy were not reported until recently in a 3-year-old child. Case report: We report a case of CES with hepatoblastoma presenting in infancy, highlighting the need to be vigilant during the follow-up of these patients. Conclusion: Our case report has possibly identified an association of malignancy with CES in infancy. Further studies linking the association of malignancy with CES may highlight the need for careful monitoring, a high index of suspicion and a low threshold for an ultrasound scan and AFP to ensure timely diagnosis and treatment.

Keywords: Cat eye syndrome, hepatoblastoma, imperforate anus

How to cite this article:
Shankar S, Hamid Al Saqban HQ, Al Zir R, Qazi A, Taylor A. Hepatoblastoma in an infant with cat eye syndrome. Hamdan Med J 2022;15:45-7

How to cite this URL:
Shankar S, Hamid Al Saqban HQ, Al Zir R, Qazi A, Taylor A. Hepatoblastoma in an infant with cat eye syndrome. Hamdan Med J [serial online] 2022 [cited 2022 May 28];15:45-7. Available from: http://www.hamdanjournal.org/text.asp?2022/15/1/45/340818

  Introduction Top

Cat eye syndrome (CES) is a rare chromosomal disorder with a highly variable clinical presentation involving multiple organs. The prevalence of the disorder is 1/50,000–1/150,000 live births.[1] The features mimic other syndromes such as CHARGE or VACTERL. Malignancy is not described as an association with CES in early infancy.

  Case Report Top

A baby boy was born at full term by normal vaginal delivery, and his birth weight was 2625 g. Mother had an uneventful pregnancy except for antenatal scans showing a single umbilical artery. He cried soon after birth, and his Apgar scores were 6 and 8 at 1 and 5 min, respectively. He developed respiratory distress soon after birth necessitating admission to the neonatal intensive care unit (NICU).

Following admission to NICU, his saturations remained low despite being on continuous positive airway pressure and 100% oxygen suggesting the possibility of congenital heart disease.

An echocardiogram showed an intracardiac total anomalous pulmonary venous connection, detailed systemic examination of imperforate anus, undescended testes with underdeveloped scrotal sac, bilateral inguinal hernia, cleft in the soft palate and bilateral preauricular pits.

Ophthalmologic examination revealed bilateral multiple small retinal haemorrhages, which resolved with no residual damage on follow-up. There was no evidence of coloboma. A mild degree of hearing loss was noted in the left ear.

There was no evidence of tracheoesophageal fistula. No limb or skeletal abnormality was detected on the skeletal survey. Ultrasound of the abdomen was normal. The baby had corrective surgery for congenital heart disease and diversion colostomy for anal atresia during the neonatal period.

Microarray assessment of the chromosomes showed a male genomic profile with a mosaic gain (2–4 copies) of 1.76 Mbp in 22q11.1q11.21 involving 29 genes. The identified mosaic partial tetrasomy contains the critical region associated with CES. This finding was consistent with CES and reflected the mosaic nature of the condition.

At 4 months of age, he presented with abdominal distention, irreducible right inguinal hernia and bluish discoloration of the scrotum. An ultrasound scan showed fluid in the scrotal sac. He underwent emergency surgical intervention for suspected incarcerated inguinal hernia and to rule out torsion of the testes as well as ischaemic bowel inside the inguinal hernia. During surgical intervention, testes were found to be viable and not in torsion. There was haemorrhagic fluid filling the scrotal cavity and hemoperitoneum. A significant part of the bowel was delivered through the hernial orifice to examine for ischaemia, and there was no evidence of ischaemia of the bowel.

The liver was found significantly enlarged and palpable to the index finger passed through the deep inguinal ring.

Computed tomography (CT) scan of the abdomen showed a solid mass in the right lobe of the liver with heterogeneous contrast enhancement [Figure 1]. His liver function test showed elevated gamma-glutamyl transferase measuring 487 U/L (NR 8–127 U/L). His total bilirubin and direct bilirubin were slightly elevated, measuring 2.62 mg/dl (NR 0.05–0.6 mg/dl) and 1.51 mg/dl (NR 0.05–0.30 mg/dl), respectively. Alpha-fetoprotein was significantly elevated, measuring more than 60,000 IU/L (NR <20 IU/L). His coagulation profile was normal. The core needle biopsy showed a predominantly epithelial component composed of small cells arranged in 2–3 cell thick cords. The cells were round to polygonal with distinct cell membranes showing no pleomorphism or hyperchromasia confirming the diagnosis of well-differentiated hepatoblastoma.
Figure 1: CT scan showing the mass in liver

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The hepatoblastoma was diagnosed to be PRETEXT III. He was treated with cisplatin as monotherapy based on the SIOPEL4 regimen. Modification to the regimen was made to avoid doxorubicin due to the cardiac condition of the infant. He continued to deteriorate with bone marrow suppression, episodes of sepsis and worsening of respiratory status requiring mechanical ventilation. The infant died 35-day post-chemotherapy at the age of around 5½ months of age.

  Discussion Top

CES is a rare condition with variable phenotype involving multiple organs and is caused by a partial trisomy or tetrasomy of the 22q11.1q11.21 region (typically due to a supernumerary marker chromosome in cases of tetrasomy). The condition is associated with many major and minor features. Major clinical features are preauricular skin tags and pits, anorectal malformation, urogenital malformation, ocular coloboma and congenital heart defects. Preauricular skin tags and pits are the most consistent feature of this condition. Ventricular septal defect and total anomalous pulmonary venous connection are the most frequently diagnosed cardiac condition.

The other abnormalities noted in this condition are cleft palate, skeletal and limb abnormalities and subtle dysmorphic features such as down-slanting palpebral fissures, inner epicanthic folds, hypertelorism, flat nasal bridge, a single umbilical artery and small mandible. Short stature due to growth hormone deficiency may be noted in some patients.[2]

In a review of 71 reported patients, the triad of preauricular abnormalities, coloboma and anorectal malformations was noted in 41% of cases. Mild-to-moderate neurodevelopmental impairment was noted in about 30% of the cases.[3]

Our patient presented with all the major features except for ocular coloboma, and he also had some of the minor clinical features associated with this condition.

Hepatoblastoma is a rare tumour that presents between 6 months and 3 years of age. It is usually sporadic, however, can be associated with genetic conditions such as Beckwith-Wiedmann syndrome and familial adenomatous polyposis. Serum alpha-fetoprotein is a key marker in the diagnosis and response to treatment. Additional imaging modalities such as ultrasound scans of the abdomen, CT or magnetic resonance imaging scans of the abdomen may be required to assess the extent of the disease.[4]

In our case, the mass in the liver was identified incidentally during the investigation for unexplained hemoperitoneum identified during surgery for suspected incarcerated hernia at the age of 4 months.

Tumours detected antenatally or after birth, up to 3 months of age are considered congenital fetal tumours.[5] Although it falls outside the age group to be diagnosed as a congenital tumour, the presentation in our case was earlier than the common age of presentation. Tumour was identified in the right lobe of the liver as is commonly noted in the literature.

To the best of our knowledge, hepatoblastoma has been reported only in 1 case of CES in a 3-year-old male in the literature. He was successfully treated with chemotherapy and surgical resection.[6]

The clinical findings were highly suggestive of CES and the chromosomal microarray confirmed the clinical diagnosis. The critical region for CES is lying with the 22pter-22q11.21 region, it is estimated approximately 2.1 Mb and contains at least 14 RefSeq genes.

In our patient, a mosaic partial tetrasomy of the CES critical region was identified through chromosomal microarray which confirmed the diagnosis. A microarray is unable to detect if the extra material was due to a supernumerary chromosome marker or another structural mechanism. Visualisation of the chromosomes through a karyotype would have determined the structure of the additional material. A karyotype was not pursued as it would not have aided in the diagnosis or care of the patient as the diagnosis was clear from the microarray report. The additional material was found to be mosaic in our patient, therefore, this tetrasomy was most likely due to a post-zygotic mutation, and therefore, the risks to future pregnancies for the parents of these individuals would be estimated to be <1%. However, there are reports in the literature of inherited mosaicism due to a supernumerary chromosomal marker.[7] Parental testing would need to be done on epithelial cells, as previous studies have suggested higher levels of mosaicism in epithelial cells vs. blood.[7]

The mosaic pattern of presentation is recognised in CES. There seems to be a direct correlation between the degree of mosaicism and the severity of symptoms ranging from no symptoms to obvious CES.[7] In our case, despite the mosaic picture, the infant presented with most of the common and consistent features of CES.

Due to the varied presentation, this condition can mimic other syndromes such as CHARGE or VACTERL syndromes. Thorough newborn examination, screening for congenital heart disorder with pre- and post-ductal saturations and ophthalmological assessment and appropriate genetic testing is necessary to make the diagnosis.

Multidisciplinary care is required to manage patients with CES.

Our case report has possibly identified an association of malignancy with CES in infancy. Further studies linking the association of malignancy with CES may highlight the need for careful monitoring, a high index of suspicion and a low threshold for an ultrasound scan and AFP to ensure timely diagnosis and treatment.

Declaration of patient consent

The authors certify that an appropriate parental consent form has been obtained with permission to use images and clinical information to be reported for the journal. The parent understands that the name of the child and theirs will not be published and due efforts will be made to conceal the identity.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Alsat EA, Reutter H, Bagci S, Kipfmueller F, Engels H, Raff R, et al. Congenital diaphragmatic hernia in a case of Cat eye syndrome. Clin Case Rep 2018;6: 1786-90.  Back to cited text no. 1
Rosias PR, Sijstermans JM, Theunissen PM, Pulles-Heintzberger CF, De Die-Smulders CE, Engelen JJ, et al. Phenotypic variability of cat eye syndrome, case report and literature review. Genet Couns 2001;12:273-82.  Back to cited text no. 2
Berends MJ, Tan-Sindhunata G, Leegte B, van Essen AJ. Phenotypic variability of Cat-Eye syndrome. Genet Couns. 2001;12:23-34  Back to cited text no. 3
Hiyama E. Pediatric hepatoblastoma: diagnosis and treatment. Transl Pediatr 2014;3:293-9.  Back to cited text no. 4
Chattopadhyay S, Mukherjee S, Boler A, Sharma A, Biswas SK. Hepatoblastoma in the neonatal period: An unusual presentation. J Cytol 2012;29:252-4.  Back to cited text no. 5
[PUBMED]  [Full text]  
McCarthy L, Flores J, Antony R, Aprahamian C, Rhee B, Reid C, et al. Hepatoblastoma associated with cat eye syndrome and congenital urogenital anomalies. Pediatric Blood and Cancer 2015;62:74-74 Poster # 652.  Back to cited text no. 6
Kvarnung M, Lindstrand A, Malmgren H, Thåström A, Jacobson L, Dahl N, et al. Inherited mosaicism for the supernumerary marker chromosome in cat eye syndrome: inter- and intra-individual variation and correlation to the phenotype. Am J Med Genet A 2012;158A:1111-7.  Back to cited text no. 7


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