Table 1 Clinical features and genotypes of 44 patients with SURF1 deficiency
From: SURF1 deficiency: a multi-centre natural history study
Case | Gender | Consanguinity | Clinical features | Age at onset* (months) | Age at death* (months) | Skeletal muscle histology/histochemistry | Muscle COX | Fibroblast COX activity | Abnormal regions on neuroimaging | SURF1 Mutations |
|---|---|---|---|---|---|---|---|---|---|---|
1a | M | Yes | PF/V, PW, nystagmus, RF | 8 | 2y 1 m | NA | NA | 29% of LLR | Cp, tectal plate, PAG, Icp, Ion, Dt, corticospinal tracts | Homo c.792_793delAG |
1b | F | Yes | PW, hypotonia, DR, DD, hypertrichosis, nystagmus, RF | 9 | 3y | T1FP, increased lipid | Low | UD | Leukoencephalopathy: WM, posterior limbs of IC, Cc, Dt, cerebellar WM | Homo c.792_793delAG |
2 | F | No | Ataxia, hypotonia, nystagmus, ophthalmoplegia, PW, tremor | 18 | Alive 12y | Smaller T1 fibres | Low | 19% of LLR | Pu, Me, Ico | c.240+1G >T, c.575G>A |
3 | F | No | DD, hypotonia, nystagmus, PW, tremor, ophthalmoplegia, ataxia | birth | Alive 19y | Normal | Low | 37% of LLR | Mb, pons | c.312_320del10insAT, c.751+5G>A |
4 | F | No | PF, movement disorder, PW, DD, RF | 7 | 16 | NA | Low | 57% of LLR | NA | Homo c.312_320del10insAT |
5a | M | No | PF, ataxia, nystagmus. ophthalmoplegia, tremor, PW, DR, RF | 10 | 5y 2 m | Absent COX, increased lipid | Low | UD | Dt, Cd, Mb, Me | Homo c.516-2A>G |
5b | M | No | PF/V DD, DR, RF | 3 days | 20 | Increased lipid | NA | NA | At 1y: normal | Homo c.516-2A>G |
6 | M | No | V, PW, hypotonia, DR, ophthalmoplegia, ataxia, encephalopathy | 9 | 21 | Increased lipid, reduced COX | NA | 12% of LLR | Dt, dorsal BS, Cp, STh | Homo c.324-11T>G |
7 | M | No | V, PW, DR, tremor, nystagmus, hypotonia, ophthalmoplegia, ataxia | 10 | 4y | Increased lipid | NA | 27% of LLR | Th, Cd, GP BS, cerebellum | Homo c.312_320del10insAT |
8a | F | No | Hypertrichosis, DD, ataxia, hypotonia, nystagmus, ophthalmoplegia, encephalopathy, PF, OA, RF | 9 | 11y 9 m | Reduced COX, T1FP, increased lipid | NA | UD | CT brain: GP and cerebellar atrophy | Homo c.516-2A>G |
8b | F | No | V, DD, PW, hypertrichosis, hypotonia, nystagmus, ophthalmoplegia, ataxia, RF | 10 | 6y 6 m | NA | NA | NA | CT brain: normal | Homo c.516-2A>G |
9a | M | No | V, PW, DD nystagmus, ophthalmoplegia, hypotonia | 2 | 24 m | Increased lipid, reduced COX. | NA | 27% of LLR | CT brain: normal | Homo c.312_320del10insAT |
9b | F | No | Hypotonia, PF/V, PW, DD, hypertrichosis, motor delay, ophthalmoplegia, RF, OA | 1.5 | 4y | NA | NA | NA | CT brain: widened subarachnoid spaces | Homo c.312_320del10insAT |
10 | M | Yes | Hypotonia, PF/V, DD, nystagmus, PW, ataxia, RF | 4 | 24 m | T1FP | Low | 50% of LLR | NA | Homo c.516-2A>G |
11 | F | Yes | DD, DR, PF/V, PW, tremor, OA, PW, hypotonia, nystagmus, ataxia, RF | 9 | 7y 1 m | Absent COX increased lipid, T1FP | NA | 7% of LLR | Mb, Dt, Cd, GP | Homo c.751C>T |
12 | M | No | PF/V, DD, DR, hypotonia, encephalopathy, PW, RF | 6 | 13 m | NA | NA | NA | Cd, Pu, BS | Homo c.312_320del10insAT, c.688C>T |
13a | F | Yes | DD, DR, PF/V, nystagmus, dystonia, PW, Sz, hypertrichosis, RF | 12 | 5y 5 m | T1FP, Reduced COX | Low | 53% of LLR | Me, Cc, cerebellar atrophy, multicystic changes in peritrigonal regions, posterior limbs of IC | Homo c.324-11 T>G |
13b | F | Yes | PF/V, PW, hypotonia, DD, DR | 15 | Outcome unknown | NA | Low | NA | NA | Homo c.324-11 T>G |
14 | F | Yes | DD, DR, hypotonia, PF/V, chorea, PW, nystagmus | 18 | Outcome unknown | Reduced COX, increased lipid | Low | UD | BG, BS, long tracts | Homo c.792_793delAG |
15 | M | No | Hypotonia, DD, DR, dystonia, ophthalmoplegia, PF/V, RF | 2y 6 m | 4y 6 m | Reduced COX, T1FP | Low | UD | BS, Calcification of Dt, Cd, GP | Homo c.312_320del10insAT |
16 | M | Yes | PF/V, PW, hypotonia, DD, DR, encephalopathy, RF | 9 | 18 m | Reduced COX. | Low | 17% of LLR | BS, Dt, SN, Pu, GP, Cd, Cc, cystic changes in Dt, BG and central WM | Homo c.324-11T>G |
17 | M | No | Short stature, ataxia, PW, hypertrichosis, nystagmus, DD | 5y | Alive 15y | Increased lipid, reduced COX | Low | NA | Dt and cerebellar atrophy | Homo c.312_320del10insAT |
18 | F | Yes | PF/V, DR, PW, DD, hypotonia, tremor, dystonia, OA, ophthalmoplegia | 10 | 8y 9 m | Absent COX T1FP | Low | 40% of LLR | Leukoencephalopathy: WM abnormalities in cerebral hemispheres and cerebellum | Homo c.833+1G>A |
19 | M | No | Hypotonia, PF/V, PW, choreoathetoid movements, dystonia, DR, RF | 10 | 3y 6 m | Reduced COX T1FP | Low | NA | Cd, Cd, GP Cp, SN. | Homo c.312_320del10insAT |
20 | M | No | Hypotonia, apnoeic episodes, motor delay, ataxia, DR, DD, tremor, hypertrichosis, dystonia, PF/V, PW, RF ophthalmoplegia, nystagmus, hypertrichosis | 10 | Alive 16y | Reduced COX | Low | NA | At 1y: normal | Homo c.704C>T |
21a | M | No | V, PW, generalized hypotonia, nystagmus, ophthalmoplegia, DD, encephalopathy, RF | 10 | 2y 3 m | Absent COX, increased lipid | Low | 23% of LLR | Pu, ventral Me, cervico-medullary region | Homo c.792_793delAG |
21b | M | No | PF/V, PW, DD, DR, hypotonia, OA, ophthalmoplegia, nystagmus, hypertrichosis, RF | 9 | 2y 5 m | NA | NA | NA | NA | Homo c.792_793delAG |
22 | M | No | DD, DR, PW, ataxia, dysarthria, choking episodes, V, hypotonia, nystagmus, hypertrophic cardiomyopathy | 4y 3 m | Outcome unknown | Absent COX | Low | NA | Deep grey matter involvement of cerebellum, Mb, Pu | c.240+1G>T, c.574C>T |
23 | F | No | PF/V, DR, DD, PW, hypotonia, nystagmus, tremor, dystonia, hypertrichosis, ophthalmoplegia, encephalopathy, ataxia, RF | 15 | 21 m | Absent COX | Low | NA | Cc, Mb, BS, GP | Homo c.312_320del10insAT |
24 | F | No | PW, V, hypertrichosis, DD, hypotonia, ophthalmoplegia, tremor, Sz, ataxia, encephalopathy, RF | 2 | 2y 10 m | Absent COX | Low | NA | Thalamic fasciculus, RN, Mb, pons, Scp, Dt, Me, WM tracts of spinal cord | Homo c.324-11T>G |
25a | M | No | PW, DD, ataxia, falls, OA, hypotonia, hypertrichosis, ophthalmoplegia, nystagmus, ataxia, RF | 20 | 14y | NA | NA | NA | Me, Icp, pons. Linear area in the periventricular WM of both occipital lobes | Homo c.871insT |
25b | M | No | DD, PF/V, PW, choreoathetosis, ataxia, hypotonia, OA, encephalopathy, ataxia, RF | 24 | 11y | Normal | NA | 30% of LLR | Cd, GP | Homo c.871insT |
26 | M | No | Hypotonia, V, PW, ophthalmoplegia, DD, nystagmus, dyskinesia, choreoathetoid movements, RF | 2 | 3y 10 m | Increased lipid | NA | UD | Cd, Cd, GP, deep WM in cerebellar hemispheres | c.312_320del10insAT, c.240+1G>T |
27 | M | No | DD, hypotonia, PF, PW, DR, RF | 10 | 4y 9 m | Reduced COX | Normal | UD | CT brain: BG | c.845_846delCT, c.240+1G>T |
28 | F | No | Hypotonia, PF/V, PW, hypertrichosis, DD, DR, encephalopathy, nystagmus | 3 | Alive 24 m | NA | NA | NA | Me, medial aspect of the cerebellar peduncles, Dt, Pu, Cp, PAG | Homo c.312_320del10insAT |
29 | F | Yes | PF, PW | birth | 24 m | NA | NA | 17% of LLR | NA | Homo c.799_800delCT |
30 | M | No | PW, DD, tremor, hypertrichosis. Post operative V, ophthalmoplegia, hypotonia | 9 days | 5y | NA | Low | NA | Ion, inferior pons, STh, Pu, spinocerebellar tracts, Icp, PAG, Dt, cerebellar WM | c.312_320del10insAT, c.871insT |
31 | F | No | PF/V, PW, DD, DR, tremor | 1.5 | 3y 7 m | Normal | Low | NA | RN, Scp, PAG, Dt, deep cerebellar WM, Me, Ion, optic radiation | Homo c.792_793delAG |
32 | F | No | PW, DD, DR, PF, hypotonia | 12 | 2y 3 m | Increased lipid | Low | NA | Mb, pons, Me, Icp, Dt, Cc, Cd, Pu, cerebellar WM, STh, SN,IC, long tracts in cervical spine | Homo c.754_755delAG |
33 | M | No | PF, PW, hypertrichosis, ataxia, DR, hypotonia, tremors, nystagmus, OA | 14 | 7y 2 m | Reduced COX | Low | 32% of LLR | Me, spinal cord, Pu, SN, IC, medullary pyramidal decussation, middle cerebellar peduncle | Homo c.312_320del10insAT |
34 | M | No | PW, PF/V, DD, DR, hypertrichosis, tremor, hypotonia, ophthalmoplegia, ataxia, RF, Sz | 13 | 24 m | Absent COX increased lipid | Low | NA | Th, Mb, dorsal pons, Me | c.312_320del10insAT, c.574insCTGC |
35 | F | No | PW, PF/V, DD, DR, hypertrichosis, hypotonia, ophthalmoplegia, OA, nystagmus, tremor, ataxia, RF, Sz | 9 | 2y 6 m | Absent COX, increased lipid | Post mortem | 12% of LLR | Th | c.312_320del10insAT, c.751C >T |
36 | F | No | PW, PF/V, DD, DR, hypertrichosis, hypotonia, ophthalmoplegia, OA, nystagmus, tremor, ataxia, RF, Sz, | 15 | 7y 10 m | Reduced COX, increased lipid | Post mortem | 44% of LLR | CT brain: Pu | c.312_320del10insAT, c.688C>T |
37 | M | No | PF, ophthalmoplegia ataxia, hypotonia,Gross motor delay, PW, DR, DD, RF, Sz, hypertrichosis | birth | 6y | Reduced COX | Low | NA | STh | c.312_320del10insAT, c. 752 -2A>G |