Table 1 Clinical and histological features of patients with RYR1 c.12083C>T (p.Ser4028Leu) mutation
From: A recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course
Family | Patient | Inheritance | Onset | First signs | Age at last examination | Signs at last examination | Age at muscle biopsy | Muscle morphology | Additional signs |
|---|---|---|---|---|---|---|---|---|---|
1 | 1 | Dominant | Childhood | Elongated face, dysmorphy, proximal muscle weakness | 72 | Proximal and distal muscle weakness, steppage gait, requires cane, difficulties climbing stairs, VC 40% | 66 | Type I fiber atrophy, fiber size variability, mitochondrial mispositioning, elongated mitochondria with crystalloid inclusions, lipid droplets | Ventricular hypertrophy |
2 | Childhood | Delayed motor milestones | 53 | Facial weakness, proximal and axial muscle weakness, difficulties climbing stairs, no running, no jumping, Gowers’s sign | - | N.A | High-arched palate, low serum CK | ||
3 | Infancy | Hypotonia, elongated face, delayed motor milestones | 14 | Proximal and axial muscle weakness, difficulties climbing stairs, no running, no jumping, hypotonia, | - | N.A | High-arched palate, low serum CK | ||
2 | 4 | Dominant | Infancy | Delayed motor milestones | 39 | Mild axial muscle weakness, myalgia, joint hyperlaxity, difficulties climbing stairs, MH episode | - | N.A | High-arched palate |
5 | Neonatal | Severe hypotonia, delayed motor milestones, recurrent infections | 3 | Axial muscle weakness, hypotonia, joint hyperlaxity, difficulties climbing stairs | 1 | Type I and II fiber atrophy | Cardiorespiratory arrest at age 4 | ||
6 | Neonatal | Severe hypotonia, delayed motor milestones, respiratory distress, recurrent infections | 5 | Axial muscle weakness, joint hyperlaxity, fatigability, difficulties climbing stairs, Gowers’s sign | 4 | Type I fiber predominance, fiber size variability | - | ||
3 | 7 | De novo | Antenatal | Hydramnios, fetal macosomia, severe neonatal hypotonia, respiratory distress, elongated face | 20 | Facial diplegia, ophthalmoplegia, axial and limb girdle weakness, difficulties climbing stairs, no running, no jumping, Gowers’s sign, VC 70% | Type I fiber predominance, lipid droplets | High-arched palate, scoliosis | |
4 | 8 | De novo | Neonatal | Hypotonia | 3 | Delayed motor milestones, joint hyperlaxity | 1 | Type I fiber predominance, rods, lipid droplets, lipofuscin granules | Pes planus |
5 | 9 | De novo | Neonatal | Hypotonia, delayed motor milestones | 16 | Mild ptosis, axial weakness, no running, no jumping, Gowers’s sign, VC 72% | 3 | Type II fiber atrophy, internal nuclei | Hallux valgus |
6 | 10 | Possibly dominant | Infancy | Delayed motor milestones, frequent falls | 48 | Ophthalmoparesis, axial and distal weakness, myalgia, steppage gait, fatigability, joint hyperlaxity, VC 75% | 28 | Type I fiber predominance, internal nuclei | High-arched palate, mild scoliosis |
7 | 11 | Possibly dominant | Infancy | Delayed motor milestones, elongated face | 43 | Mild facial weakness, mild ophthalmoparesis, axial and proximal weakness, frequent falls, fatigability, difficulties climbing stairs, myalgia, Gowers’s sign, VC 83% | 33 | Type I fiber predominance, fiber size variability, mitochondrial mispositioning | High-arched palate, mild scoliosis |
8 | 12 | De novo | Neonatal | Hypotonia, delayed motor milestones | 15 | Mild axial, girdle, and lower limb weakness, fatigability, Gowers’s sign, joint hyperlaxity | 3 | Type I fiber predominance, fiber size variability, cores | Moderate asthma, scoliosis, pes cavus |
9 | 13 | Sporadic | Infancy | Frequent falls, abnormal gait | 15 | Mild facial and limb girdle weakness, fatigability, difficulties climbing stairs, joint hyperlaxity, VC 65% | 9 | Fiber size variability, internal nuclei | High-arched palate, pes cavus |