Retinoblastoma, pinealoma, and mild overgrowth in a boy with a deletion of RB1 and neighbor genes on chromosome 13q14

Abstract

We report on a 10-year-old boy with a normal karyotype and a chromosome 13q14 deletion of the retinoblastoma gene (RB1) by fluorescence in situ hybridization (FISH). He showed subtle signs of overgrowth, including macrocephaly, hepatomegaly, and inguinal hernia. The boy also had cryptorchism and mild developmental delay. In his first months of life, variant Wiedemann-Beckwith syndrome was tentatively suspected and he was included in a careful tumor prevention program. At the age of 11 months, bifocal retinoblastoma of the left eye was diagnosed. Pinealoma was suspected at the age of 19 months and was removed by neurosurgery at the age of 29 months. At 4 years and 4 months, the deletion of the RB1 gene was suspected on clinical grounds and was diagnosed by FISH and molecular studies. At that time, he was a near-normal healthy playful kindergarten child, height 107 cm (-0.3 SD), OFC 52.5 cm (+0.8 SD), developmental age 3-3.5 years. The combination of retinoblastoma, pinealoma, and deletion of the RB1 gene diagnosed by FISH has not been reported previously. The deletion spans at least 370-420 kb in size and is predicted to include proximal and distal neighbor genes. This report may assist in establishing the clinical signs of the contiguous gene syndrome at the RB1 locus on 13q14.

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

“…31 Of note, all deletions found in our cohort are centromeric to 13q33.3q34, a region that was reported to be critical for microcephaly by Kirchhoff et al 30 Interestingly, a few patients in this cohort and in previous reports showed macrocephaly. 8,9 However, the pattern of deleted regions was the same as that in patients with normocephaly. Of note, the MTLR1/ MLNR gene, which encodes for the growth hormone secretagogue receptor found in the pituitary gland and brain, is involved in the control of growth hormone release, 32 and is deleted in 5/6 patients with macrocephaly in our cohort.…”

“…Additional case reports on patients with an interstitial 13q deletion involving band 13q14, describe macrocephaly, hypertelorism, proptosis, cleft palate, macroglossia, hypotonia and mild to severe developmental delay. [8][9][10] In two patients with Rb and an interstitial deletion extending to 13q22, Hirschsprung disease was reported. 11,12 All these patients were analyzed using standard cytogenetic analysis.…”

Brain Abnormalities on MR Imaging in Patients with Retinoblastoma

“…Disagreement was resolved by consensus. The parameters evaluated on MR imaging were selected on the basis of literature study 4,7,[12][13][14][15][16][17][18][19][20][21][22][23][24] and were divided into the following categories: benign or malignant tumor (tumor of the pineal gland, pineal cyst, or other); structural anomalies (corpus callosum agenesis, holoprosencephaly, encephalocele, Dandy-Walker malformation or a variant, hypoplasia of the basic pontis, microcephaly and polymicrogyria, or other); and degree of myelinization, ventriculomegaly, or coincidental findings. Special attention was paid to myelinization to clarify possible cognitive symptoms.…”

“…Only in case reports, describing patients with 13q deletion syndrome or in combination with retinoblastoma, are congenital brain abnormalities or brain disorders indicative of cognitive symptoms reported. 4,7,[12][13][14][15][16][17][18][19][20][21][22][23][24] Ballarati et al 25 reported central nervous system anomalies such as DandyWalker malformation, cerebellar hypoplasia, cortical dysplasia, and agenesis of the corpus callosum in patients with 13q deletion. Although one can assume that these symptoms are due to 13q deletion syndrome, it is interesting to evaluate whether (structural) brain abnormalities are involved in patients with retinoblastoma.…”

Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH

“…Afterward, a patient with a X:13 translocation and phenotypic features peculiar to the 13q14 deletion syndrome was described (Dries et al 2003). Finally, in 2004, a patient with retinoblastoma, pinealoma and mild multiple congenital anomalies/mental retardation syndrome (MCA/MR) and a germline 13q14 deletion were reported (Skrypnyk and Bartsch 2004).…”