Table 1.
Previously reported missense mutations in the HSPG2 gene in SJS and the two mutations found in our Moroccan patient (in bold). (*), mutations present in homozygous form; NR, not reported; m, month; y, year; Cbz, carbamazepine; λ, genetical aspects firstly described in Nicole et al., clinical aspects reported in Stum et al. Mx, mexiletine; Ph, phenytoin; NI, second mutant allele was not identified; UdE, undetermined effect; #, Only short stature has been reported, but no other specific skeletal abnormalities.
| Reference | N. Patient | Ethnicity | Sex | Age at onset | Mask-Like Facies | General Myotonic Signs |
Skeletal Abnormalities |
High Values of CPK | Muscle Biopsy | EMG | Medical Therapy Improvement |
Spontaneous Improvement |
cDNA Mutation HSPG2(NM_005529.7) | Effect and Domain on Protein |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nicole 2000 [5], Stum 2006 [10] λ | 2 | Tunisia | NR | pt1: 2 y pt2: 3 y |
Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.4740G > A * | UdE/III |
| Nicole 2000 [5], Stum 2006 [10] λ | 2 | Turkey | F | 1 y | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.4595G > A * | p.Cys1532Tyr/III |
| Nicole 2000 [5], Stum 2006 [10] λ | 3 | Tunisia | NR | 2.5 y | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.8464 + 4A > G * | p.Thr2773ProfsTer25/IV |
| Arikawa-Hirasawa 2002 [6] | 1 | NR | M | 3 y | Yes | Yes | Yes | Yes | NR | myotonic signs | NR | NR | 1: c.7374 + 4A > G 2: exon fusion 60–61 |
1: skip exon 56/IV 2: UdE/IV |
| Arikawa-Hirasawa 2002 [6] | 1 | NR | M | 4 m | Yes | Yes | Yes | NR | Necrotic and regenerating fibres | myotonic signs | NR | NR | 1: c.8464G > A 2: c.8759-3del9 |
1: skip exon 64/IV 2: retrain intron 66 or skip exon 67/IV |
| Arikawa-Hirasawa 2002 [6] | 1 | NR | M | 3 m | Yes | NR | Yes | NR | NR | myotonic signs | NR | NR | c.12920del7108 * | retain intron 95 or 94–95/V |
| Stum 2006 [10] | 1 | Turkey | NR | 6 m | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.574 + 481C > T * | p.Val192AlafsTer25/I |
| Stum 2006 [10] | 1 | India | NR | 2 y | Yes | Yes | Yes | NR | NR | NR | NR | NR | 1: c.665-675del 2: NI |
1: p.Arg222GlnfsTer5/II 2:NI |
| Stum 2006 [10] | 1 | Ireland | NR | 2 y | Yes | Yes | Yes | NR | NR | NR | NR | NR | 1: c.3055C > T 2: c.10355G > A |
1: p.Pro1019Leu/III 2: p.Arg3452Gln/IV |
| Stum 2006 [10] | 1 | Mauritius | NR | NR | Yes | Yes | Yes | No | NR | NR | NR | NR | c.4432C > T * | p.Arg1478Cys/III |
| Stum 2006 [10] | 1 | Turkey | NR | 6 m | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.720-1654del * | UdE/II |
| Stum 2006 [10] | 3 | Tunisia | NR | 2.5 y | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.4741-10T > G * | UdE/III |
| Stum 2006 [10] | 1 | Turkey | NR | 2 y | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | c.4648C > T * | p.Arg1550Cys/III |
| Stum 2006 [10] | 1 | France | NR | 2 y | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | 1: c.6179delC 2: NI | 1: p.Pro2060LeufsTer3/IV 2:NI |
| Stum 2006 [10] | 1 | Albania | NR | birth | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | 1: c.8680C > T 2: c.10982G > A |
1: p.Gln2894Ter/IV 2: p.Arg3661Gln/IV |
| Stum 2006 [10] | 2 | South Africa | NR | birth | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | c.7006 + 1G > A * | UdE/IV |
| Stum 2006 [10] | 2 | Brazil | NR | 9 m | Yes | Yes | Yes | NR | NR | Pt 1: doubtful neurogenic pattern Pt 2: myotonic signs |
NR | NR | c.9326delA * | p.His3109ProfsTer16/IV |
| Stum 2006 [10] | 1 | Belgium | NR | 2 y | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | 1: c.10354C > T 2: c.4432C > T |
1: p.Arg3452Ter/IV 2: p.Arg1478Cys/III |
| Stum 2006 [10] | 1 | France | NR | 4 y | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | 1: c.9642delC 2: c.7874-2A > G |
1: p.Gln3215Lysfs Ter7/IV 2: p.His2624_Val2625ins39/IV |
| Stum 2006 [10] | 1 | France | NR | 1 y | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | 1: c.10355G > A 2: c.4473_4475del |
1: p.Arg3452Gln/IV 2: p.Leu1491del/III |
| Stum 2006 [10] | 1 | The Netherlands | NR | 18 m | YES | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | 1: c.10982G > A 2: c.11192delG |
1: p.Arg3661Gln/IV 2: p.Gly373GlufsTer30/V |
| Stum 2006 [10] | 1 | Tunisia | NR | 1 y | Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | c.11208-7G > A * | UdE/V |
| Stum 2006 [10] | 4 | Saudi Arabia | NR | Pt1: 1 m Pt2: 6 m Pt3: 9 m Pt4: 2 y |
Yes | Yes | Yes | NR | NR | myotonic signs | NR | NR | c.11208-7G > A * | UdE/V |
| Stum 2006 [10] | 2 | Indian | NR | 8 m | Yes | Yes | pt1: Yes pt2: # | NR | NR | doubtful neurogenic pattern | NR | NR | 1: c.11792-11793insC 2: NI |
1: p.Leu3932AlafsTer32/V 2:NI |
| Stum 2006 [10] | 1 | Turkey | NR | 3 y | Yes | Yes | No | NR | NR | myotonic signs | NR | NR | 1: c.12191delC 2: c.4432C > T |
1: p.Pro4065ArgfsTer5/V 2: p.Arg1478Cys/III |
| Stum 2006 [10] | 1 | Turkey | NR | 3 m | Yes | Yes | Yes | NR | NR | doubtful neurogenic pattern | NR | NR | c.12899 + 1G > A * | UdE/V |
| Bauche 2013 [20] | 1 | NR | M | first 1 y | Yes | Yes | Yes | No | immunostaining: reduced perlecan in the extra-synaptic BM + fiber type I predominance | Myotonic signs | Ph/No | Yes | 1: c.2746C > T 2: c.2826 + 15G > A |
1: p.Arg916Ter/II 2: UdE/III |
| Iwata 2015 [2] | 1 | Japanese | M | 2 y 3 m | Yes | Yes | Yes | No | fiber size variation, fibre degeneration, fiber type I predominance with grouping |
myotonic signs | Cbz and Mx/Yes; Ph (s.e.) | NR | 1: c.3263T > C 2: c.9181C > T |
1: p.Leu1088Pro/III 2: p.Gln3061Ter/IV |
| Dai 2015 [22] | 1 | Chinese | F | 8 m | Yes | Yes | Yes | Yes | NR | myotonic signs | Cbz/No | NO | 1: c.5702-5G > A 2: c.10776delT |
1: UdE/IV 2: p.Ala3592fsTer6/IV |
| Bhowmik 2016 [21] | 1 | Indian | M | 2 y | Yes | Yes | Yes | Yes | NR | myotonic signs | Cbz (s.e.); Mx/Yes | NR | c.4740 + 5G > A * | p.Asp1543_Ser1580del/III |
| Padmanabha 2018 [19] | 1 | Indian | M | 2 y | Yes | Yes | Yes | Yes | NR | myotonic signs | NR | NR | 1: c.1356-10G > A 2: c.10355G > A |
1: UdE/II 2: p.Arg3452Gln/IV |
| Yan 2018 [1] | 1 | Chinese | F | 2 y | Yes | Yes | Yes | NR | NR | NR | NR | NR | 1: c.8788G > A 2: c.11671 + 5G > A |
1: p.Glu2930Lys/IV 2: UdE/V |
| Gurbuz 2019 [17] | 1 | Turkey | F | 2.5 y | Yes | Yes | Yes | NR | NR | myotonic signs | Cbz/Yes | No | c.318A > G * | UdE/I |
| Lin 2021 [18] | 2 | Taiwan | pt1: M Pt2: F |
Pt1: Childhood Pt2: NR |
Yes | Yes | pt1: Yes pt2: NR | Yes | NR | pt1: myotonic signs pt2: NR |
NR | NR | c.1125C > G * | p.Cys375Trp/II |
| This study | 1 | Marocco | M | 18 m | Yes | Yes | Yes | Yes | unspecific muscle suffering with specific aspects such as “core” | myotonic signs | Cbz/No | Yes |
1: c.3888 + 1G > A
2: c.8464G > A |
1: skip exon 31/III
2: skip exon 64/IV |