Presumed 13q deletion syndrome in a Nigerian child: A Case Report

Abstract

Introduction: 13q deletion syndrome is a rare genetic disease caused by the deletion of some or all of the long arm of chromosome 13. Patients with 13qdeletion syndrome are at risk of retinoblastoma when the RB1 gene, located in the
chromosome band 13q14 is deleted proximally. Other features include Dandy Walker malformation, cerebellar hypoplasia, and agenesis of corpus callosum.1 To the best of our knowledge, there has been no reported case in Nigerian children. We report a presumed case of 13q deletion syndrome. Case Report: We present a 3-year-old boy first seen in our facility when he was 11 months old with poor vision in both eyes noted at the age of 5 months. He is a product of twin pregnancy achieved by in vitro fertilisation and carried by a surrogate mother. He was delivered at 26 weeks
gestation with birth weight of 1.07kg, and had insertion of a ventriculoperitoneal shunt at 3 months for hydrocephalus with absence seizures. General Examination revealed plagiocephaly while systemic examination was unremarkable. Ocular examinationrevealed roving eye movements. The right eye had a central cornea opacity with no view of the fundus, left eye revealed normal anterior segment with a whitish retrolental mass. Ocular ultrasound and Magnetic resonance imaging (MRI) of the Brain and orbits revealed features suggestive of bilateral retinoblastoma
(Groups E and D in the right and left eyes respectively). His caregivers were counselled and the he subsequently underwentright enucleation (retinoblastoma was confirmed by histology [Figure 1] followed by 6 cycles of chemotherapy
(Carboplatin, Etoposide and Vincristine). He was followed up in the clinic while having chemotherapy. He defaulted follow up visits after the chemotherapy and later presented with cornealopacity in the left eye which hindered examination of the posterior segment. He subsequently had repeat MRI of the brain and orbits as well as ocular ultrasound scan, about
12 months after the initial MRI, which revealed a well defined left intraocular globular shaped retina lesion measuring 16mm by 9.5mm by 15mm (Figure 2). The child had repeat course of 6 cycles of chemotherapy (Carboplatin, Etoposide and Vincristine) and is currently being followed up in the paediatric ophthalmology and oncology units.

Discussion: Chromosome 13q deletion syndrome was first described by Allderdice after studying two paediatric patients in 19692. The first patient affected by the syndrome including retinoblastoma was reported in 19832. Clinical characteristics, phenotypic description and severity depend on the size of the deleted region and the location on the chromosome1,3. Clinical features of the syndrome vary widely among patients.Growth retardation, microcephaly, facial
dysmorphism, cardiac malformations, and mental retardation constitute the major features of the syndrome4. The syndrome is currently divided into 3 groups: Group 1 are deletions proximal to 13q32, Group 2 includes 13q 32 while Group 3 are those distal to 13q 325. Patients are at risk of retinoblastoma when the RB1 gene, located on Figure 2: T2 Weighted FLAIR MRI Brain and orbits showing enucleated right eye with prosthesis (thick blue arrow) and a well-defined left intraocular retinal based globular shaped mass (thin blue arrow). Figure 3: Absence or Agenesis of the corpus callosum. the chromosome proximally is deleted1. Distal deletion is associated with severe mental retardation but there no major malformations and growth deficiency1,6. Our patient presented with retinoblastoma, phagiocephaly, absence seizures, hydrocephalus and agenesis of corpus callosum (Figure 3) similar to features reported by Wang et
al1, Allderdice et al7, and Ballarati et al 8. Their cases also had genitourinary abnormalities and cardiac defects which were absent in our patient1. Patients with 13 q deletion are reported to presentwith corneal opacity3. Our patient had this feature which was not found in the cases reported by Wang et al1 and Gargallo et al2. The presence of retinoblastoma, agenesis of corpus callosum, little or no mental retardation and other anomalies in our patient is strongly suggestive of proximal deletion and is likely Group 1 type of 13q deletion syndrome. The features of Group 1 (proximal deletion cases) include growth deficiency, mild mental retardation, and minor anomalies. Patients with Group 1 disease can also present with microcephaly, hypertelorism, a depressed nasal bridge, simian creases, mild hypotonia and retinoblastoma5. Diagnosis is made on the basis of a thorough medical history including family medical history, physical examination, laboratory, radiological studies such as brain scan and chromosomal studies.Management of 13q deletion syndrome usually involves a multidisciplinary team of specialists.

In conclusion, although 13q deletion syndrome is a rare condition, efforts should be made to look out for features of the syndrome in patients who present with hydrocephalus and retinoblastoma. Improved access to genetic analysis may contribute to better outcomes for 13q deletion syndrome in Nigerian children.