Table 2.
Clinical Features and Protein Variants in Individuals with MACF1 Mutations
| Subject ID |
LIS with Brainstem Hypoplasia and Dysplasia |
LIS Only |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| LR14-088 | LR17-434 | LR16-306 | LR17-450 | LR04-067a1 | LR04-067a2 | LR18-077 | LR18-0704 | LR16-412 | |
| Protein Variants | |||||||||
| GenBank: NM_012090.5,a | p.Cys5177Phe | p.Cys5177Phe | p.Asp5228Tyr | p.Asp5228Tyr | p.Cys5230Phe | p.Cys5230Phe | p.Cys5230Gly | deletionb | p.Gly4706Arg |
| MACF1-204c | p.Cys7135Phe | p.Cys7135Phe | p.Asp7186Tyr | p.Asp7186Tyr | p.Cys7188Phe | p.Cys7188Phe | p.Cys7188Gly | deletionb | p.Gly6664Arg |
| Identity Data | |||||||||
| Sex | female | male | female | male | female | female | male | female | female |
| Ethnicity | C (Indian) | C (Dutch) | C (USA) | C (Polish) | C (Hispanic) | C (Hispanic) | C (Syrian) | A (Japanese) | C and A (Filipino) |
| Geographic origin | Mumbai | Rotterdam | Bay Area, CA | Warsaw | San Jose, CA | San Jose, CA | London | Saitama | Seattle, WA |
| Growth Data | |||||||||
| OFC at birth (SD) | 36 cm (+1.1) | ND | ND | 31 cm (−1)d | 32.5 cm (−1.5) | ND | ND | 33.5 cm (+0.4) | ND |
| Age at last exam | 5 years | 7.5 years | 5.5 years | 7 years | 16 years | 16 years | 7 years | 2.5 years | 5 years |
| Weight (SD) | 13.7 kg (−1.7) | 28 kg (+1) | 13.5 kg (+1.7) | 14 kg (−3) | 35.2 kg (−3) | 29.0 kg (−4) | 22 kg (−0.4) | 10.0 kg (−1.6) | 20.4 kg (+0.7) |
| Height (SD) | 105 cm (−0.5) | 128 cm (0) | 103 cm (−1) | 116 cm (−1) | 150 cm (−2) | 137 cm (−4) | 50 cm (−2) | 82.5 cm (−1.6) | 107.9 cm (−0.1) |
| OFC (SD) | 50.5 cm (0) | 53 cm (+0.7) | 45.5 cm (−1) | 47 cm (+0.5)e | 49.5 cm (−4) | 47.7 cm (−5) | ND | 47.2 cm (−0.4) | 51.3 cm (0) |
| Development and Neurological Data | |||||||||
| Developmental delay | global | global | global | global | global | global | global | global | mild |
| Hypotonia | yes | yes | yes | yes | yes | yes | yes | no | no |
| Spasticity | no | no | no | no | yes | yes | yes (legs) | no | no |
| Sitting (age) | yes (1 year) | no | no | no | yes (1 year)f | no | yes (1.5 years) | yes (1 year) | yes (7 months) |
| Walking (age) | yes (3 years) | no | no | no | yes (5 years) | no | yes (7 years)g | yes (3 years)h | yes (1.5 years) |
| Language (age) | >40 wordsi | 10 syllables | nonej | none | 3 wordsk | 3 wordsk | none | none | yes (1.5 years) |
| Intellectual disability | severe | severe | severe | severe | severe | severe | severe | severe | severe |
| Seizure onset | 5 months | 6 months | 3 months | 3 months | 7 months | 5 months | 6 months | 5 years | 4 years, 3 months |
| Seizure types | ISS | ISS, LGS | SE, LGS | MYO | FSIA, LGS | FSIA, FTCS, GTCS | probable GTCS | MYO, GTCS | FSIA, GTCS |
| Dyskinesial | hand flapping | mixed | ND | no | mixed | mixed | mixed | hand waving | no |
| Vision abnormalities | CVI, left ONH | no | CVI | no | normal | normal | ND | ND | normal |
| Eye movements | abnormal NOS | abnormal NOS | normal | no | nystagmus horizontal | ND | slow tracking | abduction limitedm | normal |
| Strabismus | left exotropia | exotropia | ND | no | ND | esotropia | ND | ND | no |
| Feeding abnormality | none | impaired, GT | impaired, GT | no | ND | ND | none | none | no |
| Other | |||||||||
| Feature | VSD closed | none | none | none | none | none | dysmorphicn | none | none |
Abbreviations are as follows: A, Asian; C, Caucasian; CVI, cortical visual impairment; FSIA, focal seizure with impaired awareness; FTCS, focal tonic-clonic seizure; GT, gastrostomy tube; GTCS, generalized tonic-clonic seizure; ISS, infantile spasm; LGS, Lennox-Gastaut epilepsy syndrome with atonic, tonic, tonic-clonic, and myoclonic seizures; MYO, myoclonic seizure; ND, no data available; NOS, not otherwise specified; OFC, occipitofrontal circumference; ONH, optic-nerve hypoplasia; SD, standard deviation; VSD, ventriculoseptal defect.
GenBank: NM_012090.5 and transcript MACF1-203 (Ensembl: ENST00000361689.6).
Deletion of exons 58–89 (p.Ala3540_Arg5192; GenBank: NM_012090.5) or exons 62–93 (p.Ala5498_Arg7150; MACF1-204).
Transcript MACF1-204 (Ensembl: ENST00000372915.7).
OFC at 36 weeks of gestation.
OFC at 1 year.
Sits with support only.
Few steps only.
Walks with support at 3 years.
Also with several word combinations.
Uses Picture Exchange Communication System (PECS).
Words later lost.
Mixed abnormal movements with combinations of chorea, athetosis, dystonia, and (in the twins) ballismus.
Ocular abduction limited to half normal excursion at 2.5 years but improved to normal abduction by 5 years.
Hypertelorism, low nasal bridge, epicanthal folds, and low-set ears.