Case Report: The Emerging Role of Ring Chromosome 22 in Phelan-McDermid Syndrome With Atypical Teratoid/Rhabdoid Tumor: The First Child Treated With Growth Hormone

Abstract

Atypical teratoid/rhabdoid tumors (AT/RTs) in the rhabdoid tumor predisposition syndromes are most often caused by germline mutations of the SMARCB1 gene located in chromosome 22q11.2. Although rarely, it can also result from the constitutional ring chromosome 22 (r22): during mitosis the ring chromosome may lead to an increased rate of somatic mutations, resulting in rhabdoid tumor predispositions when the tumor-suppressor gene SMARCB1 is involved. Individuals with r22 may present similar features as those with Phelan-McDermid syndrome (PMDS) due to 22q13.3 deletion, including the SHANK3 gene. Despite several reports on AT/RT in children with r22 and/or PMDS have been published, the role of constitutional r22 as new oncogenic mechanism for AT/RT is still under investigation. There is not a lot of data available on therapeutic and prognostic implications of r22 in AT/RT and PMDS. Herein, we present the first case of a child with constitutional r22, PMDS and AT/RT of the brain, who is a long term survivor and is been treated with growth hormone. We also describe an unexpected adverse reaction to midazolam.

Atypical teratoid/rhabdoid tumour‐TYR subtype arising in the setting of germline ring chromosome 22: An uncommon form of tumour predisposition

“…In ATRT patients with somatic SMARCB1 inactivation and wildtype germline SMARCB1, germline karyotype and chromosomal microarray could be considered, especially for patients with dysmorphic features, developmental delay, or disproportionate growth. Furthermore, given that the phenotypic spectrum associated with germline ring chromosome 22 is broad [2,16], including some with mild features [2,7,16], and one incidentally found adult with r(22) lacking disruption of SHANK3 [2,16], germline chromosomal microarray could also be considered for all ATRT patients with loss of chromosome 22 observed in the tumour. For patients in which germline chromosomal microarray demonstrates a terminal deletion involving 22q, subsequent germline karyotype analysis would be appropriate to evaluate for r(22).…”

“…A small number of patients (five) with germline ring chromosome 22 and ATRT have previously been characterised [1, 6–9] (Table S1) with a variable degree of molecular analysis and reported outcomes [10], with now seven molecularly confirmed cases when including the two cases reported here. The true incidence may not be fully recognised as germline karyotype evaluation is not routine in ATRT patients.…”

Molecular cytogenetic and phenotypic characterization of Phelan McDermid and 22q13 duplication syndrome: a case report

“…According to the mosaic status in different tissues, various phenotypic deviations may be observed in basically similar r(22) cases [ 14 ]. According to [ 15 ] r(22) has been seen to be associated with PHMDS in at least 5 cases, yet. Here we report another such case, which was not suspected to be PHMDS, before a r(22) was observed in banding cytogenetics.…”