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.
Highlights
Atypical teratoid/rhabdoid tumors (AT/RTs) represent 20% of highly malignant tumors of the central nervous system (CNS), in children < 3 years old [1].The SMARCB1/INI1 gene codes a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, actin-dependent chromatin remodeling complex and is known to act as a tumor suppressor
The presence of the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) protein does not rule out a diagnosis of AT/RT [4]
In our clinical case SMARCB1 was not mutated in the germline DNA and the partial deletion of chromosome 22 not involving the SMARCB1 gene, the immunohistochemistry of the AT/RT tumor of our patient demonstrated the absence of the SMARCB1 protein (Figure 3B), suggesting the loss of both alleles
Summary
Atypical teratoid/rhabdoid tumors (AT/RTs) represent 20% of highly malignant tumors of the central nervous system (CNS), in children < 3 years old [1]. After 18 months of treatment, the growth velocity remained consistently regular (6.2 cm/year, −0.8 SDS); IGF-1 increased from 47.6 ng/ml (−3.8 SDS) to 78.1 ng/ml (−2.3 SDS) 6 months after hrGH initiation (0.028 mg/kg/day), reaching normal values up to 146.2 ng/ml (−0.55 SDS) after a further 18 months of treatment (0.031 mg/kg/day) The latter dose is currently ongoing without side effects. As for institutional protocol, intranasal midazolam was implemented to increase the patient’s compliance to procedural sedation for MRI; shortly after midazolam was administered for the first time to our patient (months before starting hrGH) he showed signs of shock (severe hypotension, prolonged capillary refill time, a decreased level of consciousness and urinary output, and bradycardia) and needed resuscitation.
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