Table 1 Studies describing the 17p13.3 duplication/ triplications associated with SHFM or SHFLD
Reference [No.] | No. of families/ individuals with duplication/ triplication (a) | Limb anomalies of affected individuals | Extra-limb manifestations | Special remarks |
|---|---|---|---|---|
ezirovitz et al., 2008 [3] | 1 family 9 affected individuals | SHFM (4), SHFLD [tibial hemimelia] (3), Tibial hemimelia/aplasia only (2) | No | Autosomal dominant (AD) inheritance/ Variable expressivity (VE)/, Incomplete penetrance (IP), Defined candidate region to 17p13.1 – 17p13.3; ~ 861 kb |
Armour et al., 2011 [4] | 3 families (?1 with triplicationa) with 12 affected individuals 7 with duplication: 6 affected, 1 unaffected | Split hand only (3), SHFLD [tibial hypoplasia/aplasia] (9) | No | AD inheritance/ VE/ IP Defined critical region of ~ 173 kb, ?BHLHA9 or AC016292 duplication |
Klopocki et al., 2011 [5] | 17 families (out of 56) 82 with duplication: 42 affected, 40 unaffected | SHFLD [tibial hemimelia] (18/31) Only SHFM (5) | No | AD inheritance/ VE/ IP Sex bias: (Male>Female), affected females with more severe phenotype Defined critical region of ~ 11.8 kb encompassing only BHLHA9 gene |
Petit et al., 2013 [7] | 2 affected with duplication | Case 1 SHFLD [R/radial agenesis and hypoplastic R/ulna and L/radial hypoplasia] Case 2 SHFM only | Case 1 small ASD | Involvement of radius reported for the first time |
Curry et al., 2013 [8] | 1 affected 14 families in this report (total of 21 families analyzed) with 17p13.3 duplications that includes BHLHA9 | SHFLD [tibial hemimelia] | Cleft palate, Mild ID | |
Luk et al., 2014 [9] | 1 affected fetusa Unaffected mothera both with duplication | Split hands | No | First case with prenatal genetic diagnosis |
Petit et al., 2014 [10] | 13 families with 42 affected individuals and 19 unaffected obligate carriers; 29 with the duplication (20 affected, 9 unaffected) | SHFLD (18) | No | AD inheritance/ VE/ IP Involvement of radius in 2 individuals Femur hypoplasia in one patient Affected males with more severe phenotype |
Al Kaissi et al., 2014 [11] | 1 affected Father- bilateral partial syndactyly | SHFM, tibial hemimelia | Sacral hypoplasia, DD, Thrombocyto-penia | |
Nagata et al., 2014 [12] | 27 families 64 with the duplication/triplication (42/42 affected patients, 22/47 unaffected relatives); 2/1000 Japanese controls positive for duplication | SHFM (29), SHFLD (11), GWC (2) | NR | No sex bias SHFLD and GWC more common in triplications |
Nagata et al., 2015 [13] | 1 affected childa Unaffected mothera both with triplication | SHFM with tibial aplasia (R)/ hypoplasia (L) and wide R/ distal femoral metaphysis (GWC-like malformation) | No | |
Cho et al., 2015 [14] | 1 affected fetus with the duplication | SHFLD, campomelia of R/femur, Bilateral agenesis of fibula, bilateral club feet, oligosyndactyly | No | |
Fusco et al., 2017 [15] | 3 affected with the duplication | SHFLD; tibial hypoplasia (2) One with isolated tibial hypoplasia | One with ASD | |
Shen et al., 2018 [16] | 1 family with 5 affected individuals, 4 affected fetuses 10 tested (8 individuals, 2 fetuses) 8 with the duplication; 6 affected, 2 unaffected | SFFM (4) SHFLD (1), bilateral femoral hypoplasia | No | |
Present report 2018 | 1 affected child Affected mother | SHFM (?with tibial hemimelia) | No |