Table 1 Summary of clinical features of individuals with bi-allelic ATG4D variants.
Clinical feature | Individual 1 (Family 1: II-2) | Individual 2 (Family 2: II-3) | Individual 3 (Family 2: II-4) |
|---|---|---|---|
Demographics | |||
Sex | Male | Female | Female |
Ethnicity | European | Tatar/Russian | Tatar/Russian |
Age of onset | 2 years | 9 months | 18 months |
Chief complaint | Episodic dyscoordination and gait abnormality, staring episodes, and mild speech and motor developmental delay | Abnormal hand movements and staring episodes (concern for seizures), gait abnormality, mild speech and motor developmental delay | Mild speech and motor developmental delay |
Prenatal and perinatal history | |||
Gestation at delivery | Full term (40 weeks) | Early term (37 weeks) | Preterm (32 weeks and 5 days) |
Delivery | Vaginal delivery (pitocin induction) | Elective C-section | C-section for preterm labor and fetal distress |
Birth weight | 3500 g (44th percentile) | 3500 g (91st percentile) | 2263 g (86th percentile) |
Birth length | 53.0 cm (79th percentile) | NA | 46.0 cm (92nd percentile) |
Head circumference | 36.2 cm (79th percentile) | NA | 32.5 cm (98th percentile) |
Growth parameters | |||
Age at measurement | 5 years 3 months | 4 years 8 months | 3 years 5 months |
Weight | 20.7 kg (74th percentile) | 16 kg (29th percentile) | 15 kg (58th percentile) |
Height | 114.0 cm (77th percentile) | 107.6 cm (69th percentile) | 96.0 cm (42nd percentile) |
Physical findings | |||
Characteristic facial features (almond-shaped eyes, depressed nasal bridge, and prominent Cupid’s bow) | + | + | + |
Auricular tag | + (left) | − | − |
Ophthalmological findings | |||
Hyperopia, amblyopia, astigmatism | + | − | − |
Musculoskeletal findings | |||
Muscular hypotonia | + | WNL | WNL |
Distal muscle weakness | + (progressive, age at onset: 3 years) | Not observeda | Not observeda |
Neurological findings | |||
Abnormal gross motor development | + (slow, progressive decline) | +/− (delayed: crawled at 12 months, walked at 20 months, ran a little at 2 years 10 months; resolved by 4 years 8 months) | + (delayed; walked at 19 months) |
Speech impairment | + (speech delay and dysarthria) | + (speech delay with 1st word at 12 months/3 words at 21 months; poor speech articulation at 4 years 8 months) | + (speech delay with 1st word at 12 months/2 words at 20 months; poor speech articulation at 3 years 5 months) |
Mild cognitive impairment | + | + | Not observeda |
Abnormal gait | + (frequent falls and clumsiness, age at onset: 2 years; progressive unsteady gait, age at onset: 4 years) | +/− (shuffling gait, frequent falls/tripping, and clumsiness at 25 months and at 2 years 10 months, resolved by 4 years 8 months) | Not observeda |
Abnormal eye movements | + (saccadic intrusions and central nystagmus) | Not observeda | Not observeda |
Intention tremor | + (bilateral, progressive) | Not observeda | Not observeda |
Poor fine motor coordination | + | Not observeda | Not observeda |
Decreased DTRs | + (0 at patella and ankles) | +/− (1+ at patella at 25 months, 2+ at 4 years 8 months) | Not observeda |
Mild sensory neuropathy | + | Not examined | Not examined |
Oppositional defiant disorder | + | Not observeda | Not observeda |
ADHD-PI | + (diagnosed at 7 years) | Not observeda | Not observeda |
Hypersomnolence | + (age at onset: 4 years) | Not observeda | Not observeda |
Seizures | + (initially generalized, followed by focal) (described as focal absence) | +/− (concern due to staring episodes at 25 months, resolved by 4 years 8 months) | Not observeda |
Abnormal EEG findings | + (multifocal abnormalities, high risk for focal and generalized epilepsy at 3.5 years; prolonged EEG normal at 5 years 3 months) | WNL at 1 year 8 months | ND |
Neuroimaging findings | |||
MRI | Non-progressive mild cerebellar atrophy of the superior cerebellar hemispheres and vermis | WNL at 1 year 3 months | ND |
MRS | Elevated choline in 5 of 6 locations | ND | ND |
