Table 1 Clinical description of the four ARCA-affected individuals
From: A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder
Affected individuals (year of birth) | |||||
|---|---|---|---|---|---|
V-9 (2004) | V-10 (2000) | V-12 (2001) | V-14 (1999) | ||
Karyotype | 46, XX | 46, XX | 46, XY | 46, XY | |
Pregnancy and delivery | Uncomplicated | Uncomplicated | Uncomplicated | Clomid-induced but uncomplicated | |
GA at delivery | 36.5 weeks | 38 weeks | 39 weeks | 39 weeks | |
Weight at birth | 2455 g (10th percentile) | 2610 g (10th percentile) | N/A | 2550 g (<3rd percentile) | |
Length at birth | 47.5 cm (25th percentile) | N/A | N/A | N/A | |
HC, at birth * | 30 cm (<3rd percentile) | N/A | N/A | N/A | |
Fontanelle closure | at 6.5 mo: Anterior open (N), posterior closed (N) | at 2 mo: Anterior closed (abN) | at 5.5 mo: Anterior closed (abN) | at 8 mo: Anterior fontanelle closed | |
Status | died at 18 months | died at 2 years | alive at 12 yrs | alive at 14 yrs | |
Autopsy | - | + | - | - | |
Development milestones | Suckling | stopped by 6 weeks | stopped by 5 mo | N/A | N/A |
Smile | started at 2 mo, stopped by 7 mo | Started at 2 mo, stopped by 3 mo | no reflexive smile at 1 mo | Started at 2 mo, stopped by 4 mo | |
Sitting | unable at 7 mo | unable at 8 mo | unable at 4 yrs | unable at 5 yrs | |
Babbling | unable at 7 mo | unable at 8 mo | no speech at 4 yr | N/A | |
Neurological signs | Seizures/Epilepsy | - | + | + | + |
EEG | N/A | marked abnormality with low cortical activity, no epileptiform activity noted | generalized central epileptiform activity | Grade 1 generalized and suppressed cerebral activity | |
Spasticity | + (fisted hands, legs scissoring) | + (legs scissoring, arms stiff) | + (myoclonic spasm due to sound/light touch, fisted hands) | + (clonus of R ankle) | |
Reflexes | N/A | brisk, clonus of L ankle | unable to assess | hyperreflexia | |
Tone | hypotonic trunk, hypertonic extremities | Hypotonic lower extremities | hypotonic trunk, hypertonic extremities | hypertonic extremities | |
Irritable | ++ | ++ | +++ | +++ | |
Head circumference, last recorded | 36.5 cm @ 6.5 mo (<3rd percentile) | 35.5 cm @ 2 yrs (<3rd percentile) | 43.3 cm @ 4 yrs (<3rd percentile) | 39 cm at 8.5 mo (<3rd percentile) | |
Akathisia | + | + | ++ (while awake) | ++ | |
Startles | easily | easily | easily however less pronounced presently | easily however less pronounced presently | |
Vision and Hearing | Visual impairment | inconsistent with cues | infrequent, strabismus | cortical, horizontal + vertical nystagmus | cortical visual impairment, eyes roll back |
Fundoscopy | N/A | N/A | mild atrophic fundi | hypoplastic optic nerve and fovea | |
Hearing | Normal | normal | normal | normal | |
Other organs | G-tube | - | at 1 yr | at 4 yrs due to recurrent aspiration pneumonitis | - |
Abnormal Bloodwork | Elevated ammonia, Mn, lactate, platelets | Elevated Mn, lactate, and platelets | Elevated CK, CK-MB, and platelets | ||
MRI | Age at time of imaging | 10 mo | 8 mo, 11 mo, | 3 mo, 12 mo | 7 mo, 13 mo, 6 yrs 7 mo |
Description | Severe symmetrical cerebral volume loss, gray and white matter affected, thinned corpus callosum. Cerebellum, brainstem, midbrain and supratentorial deep grey matter are unaffected. | Enlarged lateral and 3rd ventricles, severe uniform atrophy of the brain with subcortical white matter loss. Normal spine to T2, cerebellum and pons. | Marked progressive cerebral and cerebellar atrophy with basal ganglia involvement | Prominent ventricles, thin white and grey matter | |
CT | Age at time of imaging | 6 mo | 3 mo | ||
Description | Prominent subarachnoid spaces and ventricular system. Infratentorial compartment is normal, including cerebellum and 4th ventricle | Generalized cerebral atrophy with associated ventriculomegaly, difficult to differentiate between grey/white matter | |||