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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  
  1. * Based on: Barbier et al, 2013. Pediatrics. “New Reference curves for Head Circumference at Birth, by GA”. Abbreviations: N/A, not available; "-", not determined.