Table 2.
Clinical Features in Kindreds Affected by BICD2 Mutations
|
Kindred |
||||||
|---|---|---|---|---|---|---|
| AUS1 | AUSTRIA1 | USA1 | UK2 | UK1 | GERMANY1 | |
| Mutation | c.320C>T (p.Ser107Leu) | c.320C>T (p.Ser107Leu) | c.320C>T (p.Ser107Leu) | c.565A>T (p.Ile189Phe) | c.1502G>C (p.Arg501Pro) | c.1523A>C (p.Lys508Thr) |
| Clinical phenotype | DCSMA | DCSMA | DCSMA+UMNa | DCSMA+UMNa | DCSMA+UMNa | HSP |
| Number of generations in pedigree | 4 | 3 | 4 | 2 | 3 | 3 |
| Number of affected and unaffected individuals (clinically confirmed) | 6 (4) | 5 (3) | 4 (4) | 1 de novo (1) | 5 (5) | 4 (1) |
| Congenital and Early-Onset Contracture Dislocations | ||||||
| Congenital hip dysplasia and/or joint dislocation | 1 | 0 | 2 | 1 | 1 | 0 |
| Congenital or early-onset hip contracture | 1 | 0 | 0 | 1 | 0 | 0 |
| Congenital or early-onset knee contracture | 2 | 0 | 0 | 1 | 0 | 0 |
| Congenital or early-onset Achilles tendon contractures | 2 | 2 | 0 | 1 | 5 | 0 |
| Congenital talipes or early-onset deformities | CV = 4, EV = 0 | CV = 2, EV = 0 | CV = 0, EV = 0 | CV = 1, EV = 0 | CV = , EV = 2 | CV = 0, EV = 0 |
| Foot Features and Abnormalities | ||||||
| High arch (H), pes cavus (C), or pes planus (P) | H = 0, C = 0, p = 4 | H = 0, C = 0, p = 0 | H = 0, C = 3, p = 0 | H = 0, C = 0, p = 0 | H = 1, C = 0, 1 p = 0 | H = 1, C = 1, p = 0 |
| Lower-Limb Features: Weakness and Wasting | ||||||
| Proximal = distal weakness | 3 | 3 | 2 | 1 | 2 | 1 |
| Proximal > distal weakness | 0 | 0 | 2 | 0 | 0 | 0 |
| Distal > proximal weakness | 1 | 0 | 0 | 0 | 2 | 0 |
| Proximal = distal wasting | 3 | 3 | 2 | 0 | 3 | 0 |
| Proximal > distal wasting | 0 | 0 | 1 | 0 | 0 | 0 |
| Distal > proximal wasting | 1 | 0 | 1 | 1 | 1 | 1 |
| No weakness or wasting but other features (e.g., contractures) | 0 | 0 | 0 | 0 | 1 | 0 |
| Adult-onset lower-limb contractures, weakness, and wasting | 0 | 0 | 0 | NA (child) | 0 | hip, Achilles tendon |
| Lower-Limb Deep-Tendon Reflexes | ||||||
| Reduced or absent in lower limbs | 4 | 2 (not tested in the third) | 1 | 1 | 1 | 0 |
| Increased in lower limbs | 0 | 0 | 0 | 0 | 2 | 1 |
| Mixed (reduced and increased) in lower limbs | 0 | 0 | 2 | 0 | 2 | 0 |
| Plantar Responses | ||||||
| Normal | 4 | 2 (not tested in the third) | 4 | 0 | 3 | 0 |
| Upgoing or equivocal | 0 | 0 | 1 | 1 | 2 | 1 |
| Upper-Limb Features: Weakness and Wasting | ||||||
| Mild weakness in one or more regions | 0 | 2 (shoulder, hand) | 3 (shoulder, fingers) | 1(elbow) | 2 (scapular winging) | 0 |
| Mild wasting in one or more regions | 0 | 2 (shoulder, hand) | 0 | 0 | 0 | 0 |
| No weakness or wasting | 4 | 1 | 1 | 0 | 0 | 1 |
| Adult-onset upper-limb contractures, weakness, and wasting | 0 | 0 | 0 | NA (child) | 0 | 0 |
| Upper-Limb Deep-Tendon Reflexes | ||||||
| Reduced or absent in upper limbs | 1 | 2 (not tested in the third) | 0 | 0 | 0 | 0 |
| Increased in upper limbs | 0 | 0 | 0 | 1 | 5 | 1 |
| Mixed in upper limbs | 0 | 0 | 0 | 0 | 0 | 0 |
| Motor Development and Ambulation | ||||||
| Delayed early motor milestones | 4 | 1 | 4 | 1 | 2 | 0 |
| Wide-based gait and/or hyperlordotic gait | 2 | 2 | 1 | 1 | 1 | 0 |
| High-stepping gait | 0 | 3 | 0 | 0 | 0 | 0 |
| Fatigues quickly when walking and falls often | 3 | 1 | 2 | 1 | 4 | 1 |
| Uses orthoses and/or walking aide, including frame | 2 | NA | 3 | 0 | 0 | 1 |
| Uses wheelchair | 2 | 1 | 0 | 1 | 1 | 2 |
| Respiratory Abnormalities | ||||||
| Obstructive sleep apnea symptoms and/or signs and/or need for NiPV | 3 | − | 1 | 0 | 0 | − |
| Restrictive lung disease and/or reduced FVC | 0 | − | 1 | 0 | 0 | − |
| Other Clinical Features | ||||||
| Vibration abnormality (V) and/or foot paraesthesias (P) | 0 | 0 | 3 (V: 1 with diabetes) | 0 | 0 | 1 (V and P) |
| Mild to moderate intellectual disability | 1 | 0 | 0 | 0 | 1 | 0 |
| Scoliosis (S), kyphosis (K), pectus excavatum (P), bulbar weakness (B) | S = 1, K = 0, p = 1, B = 1 | S = 1, K = 0, p = 0, B = 0 | S = 0, K = 1, p = ?, B = 0 | S = 0, K = 0, p = 0, B = 0 | S = 0, K = 1, p = 0, B = 0 | S = 0, K = 0, p = 0, B = 0 |
| Surgery Required | ||||||
| Surgical relocation of one or both hip and/or femoral osteotomies | 1 | − | 0 | 1 | 1 | 0 |
| Tendon-release surgery on foot and/or other lower limb | 1; 2 planned | − | 0 | 1 | 3 | 0 |
Shown are the clinical features in six kindreds affected by DCSMA, HSP, or DCSMA+UMN due to BICD2 mutations. Abbreviations are as follows: CV, calcaneovalgus; EV, equinovarus; NA, not available; NiPV, noninvasive pulmonary ventilation; and FVC, forced vital capacity.
a
UMN signs present in lower limbs, upper limbs, or both in at least one affected kindred member.