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22q11.2 recurrent region (distal type III, D-G/H) (includes SMARCB1) |
- 3
Haplo
Score - 0
Triplo
Score
Dosage Sensitivity Summary (Region)
Dosage ID:
ISCA-46292
Curation Status:
Complete
Issue Type:
Dosage Curation -
Region
Description:
The 22q11.2 region contains a cluster of low copy repeats that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to distal region CNVs involving recurrent breakpoints LCR22-D and LCR22-G or -H, often referred to in the literature as the distal type III region. The 22q11.2 D-G region is also known as LCR22 4-7 in some older literature. Smaller, fully encompassed CNVs, such as those involving the F-G or E-F regions, are reviewed separately.
Note that genes used as landmarks are not necessarily causative of the phenotype(s) associated with the region.
NOTE: Curation of overlapping CNVs involving the LCR22-D to -E or -F (distal type I), the LCR22-E to -F (distal type II), LCR22-F to -G (distal type III), and the LCR22-E or -F to -H (distal type III) regions are linked below.
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
03/27/2023
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- rhabdoid tumor predisposition syndrome 1 Monarch
HI Evidence:
-
PUBMED:
21671380
Tan et al. (2011) report a patient with a de novo 22q11.2 D-G deletion. The clinical findings reported in this individual include development/cognition issues, behavioral problems (immature, poorly attentive, hyperactive), hearing loss, postnatal growth failure, microcephaly, flat midface, long smooth philtrum, thin upper lip, micro/retrognathia, and bilateral ear tags. The patient was also reported to have an epibulbar dermoid, hemifacial microsomia, and neonatal hypoglycemia.
-
PUBMED:
21187175
Beddow et al. (2011) report a patient with a de novo 22q11.2 D-G deletion. The clinical findings reported in this individual include language delay, Tourette syndrome, dyspraxia, ADHD, dilated cardiomyopathy, long/asymmetrical face, small mouth, long fingers, camptodactyly of the toes, and an atypical teratoid/rhabdoid tumor (AT/RT) which localized to the cerebellar vermis.
-
PUBMED:
17541642
Jackson et al. (2007) report 2 patients with 22q11.2 D-G deletions. The clinical findings reported in these individuals include developmental delay, hearing loss, cleft palate, cardiac anomalies (VSD/ASD), mild facial asymmetry, short upslanting palpebral fissures, malar flatness, and fifth finger clinodactyly. Both patients were also found to have rhabdoid tumors, with one having a left renal rhabdoid tumor which had metastasized to the heart and lungs, and the other having a “mass encasing the spinal cord and nerve roots from T12 to the sacrum.” Inheritance information was not provided. This study also reported 3 additional patients with smaller, overlapping, atypical deletions with at least one breakpoint between LCRs. Limited clinical information was available for these patients; however, all 3 were reported to have rhabdoid tumors.
HI Evidence Comments:
At least 10 deletions involving the distal 22q11.2 D-G/H region have been reported in the literature (9 D-G and 1 F-G). Several non-LCR22-flanked deletions overlapping this region have also been reported. The clinical findings associated with distal type III deletions include variable dysmorphic features, developmental delay, hearing loss, and cardiac defects. Due to the involvement of SMARCB1, deletions of this region are also commonly reported in association with the development of rhabdoid tumors early in life. Parental testing has been performed in 6 patients with 22q11.2 D-G/H deletions and in all cases, it was found to represent a de novo event.
Additional relevant literature is summarized below:
PMID: 19938088
Lafay-Cousin et al. (2009) report a patient with a de novo 22q11.2 D-G deletion. The clinical findings reported in this individual include hemifacial microsomia, preauricular skin tags, long/smooth philtrum, thin upper lip, downturned corners of the mouth, and an epibulbar dermoid cyst. At one year of age, the patient was found to have an atypical teratoid/rhabdoid tumor (AT/RT).
PMID: 21412926
Toth et al. (2011) report a patient with a 22q11.2 D-G deletion. The clinical findings reported in this individual include bilateral cleft lip/palate, bilateral ear tags, club feet, VSD, a “well-demarcated vascular-appearing growth” on his shoulder, and a violaceous nodule. The patient was also reported to have bilateral axillary malignant rhabdoid tumors. Inheritance information was unavailable.
PMID: 21208904
Bourdeaut et al. (2011) report 3 patients with 22q11.2 D-G/H deletions (2 D-G and 1 F-G). Limited clinical information was available for these patients; however, all 3 were reported to have rhabdoid tumors.
PMID: 15957176
Wieser et al. (2005) report a patient with a de novo 22q11.2 D-G deletion. Note that this patient was also found to have an adjacent 22q11.2 duplication that was 2.8 Mb in size. The clinical findings reported in this individual include developmental delay, hearing issues, VSD, and dysmorphic features. At 9 months of age, he was also found to have a highly malignant rhabdoid tumor.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time duplications involving 22q11.2 distal breakpoints D and G/H have not been reported in the literature. Overlapping duplications involving breakpoints E/F and H have been reported and are reviewed separately in the 22q11.2 recurrent region (distal type III, E/F-H) review.
