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Case Reports
Table 1. Clinical, neuroimaging and molecular findings in patients carrying pathogenic IARS2 variants.
Authors, year
Schwartzentruber et al., 2014
Pt Sex Family
1F 1
2F 1
3M 1
4 M 2
1 F 1
1 F 1
2 F 1
1 M 1
2 F 2
3 F 2
1 M 1
2 M 2
Diagnosis
CAGSSS
CAGSSS
CAGSSS
Age at onset
Birth
Birth
Birth
Neurological findings and development
DD, distal sensory neuropathy (9,5 y)
DD, distal sensory neuropathy (8 m)
DD, distalsensory neuropathy
Ocular findings
Cataract (17 m), corneal opacification (5y), orbital myopathy (32 y)
IARS2
mutations
Homozygous c.2726C>T (p.Pro909Leu)
Homozygous c.2726C>T (p.Pro909Leu)
Homozygous c.2726C>T (p.Pro909Leu)
Moosa et al., 2017
Takezawa et al., 2018
syndrome
CAGSSS Birth
Hypotonia,
peripheral neuropathy
Infantile spasms, DD
Infantile spasms
Spasticity
No
No
Cataract
(3 y)
Cataract (8 y)
No
Congenital
Normal GH Bilateral
Short stature hip
atrophy and hyperintensities on T2 in the basal ganglia and thalami Mild hydrocephalus and narrow foramen magnum
Hearing
loss (8 y)
(deceased)
8 y
No ID
heterozygous c.1821G>A (p.Trp607*) and c.2122G>A (p.Glu708Lys) Homozygous c.2620G>A (p.Gly874Arg)
Compound heterozygous c.680T>C
CSF L
Dysmorphic
features Telangiectasia
Increased L and L/P in blood and CSF
Increased L and L/P in blood and CSF
Type 2
achalasia, dysmorphic features Dysmorphic features
Dysmorphic features
Increased serum L
Cataract (3 m), corneal opacification (17y)
GH deficiency Bilateral
Endocrinological Skeletal findings
Brain MRI
Atrophied pituitary
Auditory features
hearing loss (2 y)
Hearing loss
Hearing loss(21m) NoID
and growth
GH deficiency (15 y) Short stature
Bilateral hip
Follow-up
33 y No ID
6 y No ID
Other
Dysmorphic features. Type 2 achalasia
Dysmorphic features
Dysmorphic features
(4 y) Short stature
hip dislocation, SEMD (18 m)
Cataract (5 m), GH deficiencyBilateral hip
17 y
corneal opacifications (5 y)
(5y) Short stature
dislocation (at birth), SEMD
dislocation, adenohypophysis
SEMD (2 y)
and small neurohypophysis
Leigh 1m No No No No Diffuse No 18m Compound Increased
CAGSSS, Leigh and West syndrome
(-6SD)
Short stature (-5 SD)
dislocation (at birth), SEMD (18 m) NK
Vona et al., 2018
Li et al., 2018
CAGSSS, Leigh and West syndrome
CAGSSS
CAGSSS
CAGSSS
Cataract
Cataract
NK NK Short stature
(-5 SD)
GH SEMD
bilateral hyperintensity in the basal ganglia on T2 (18 m) Normal
NK
NK
(p.Arg817His) 5 y Hypotonic quadriplegia, bedridden (1 y)
20 y
No ID
35 y No ID
27 y No ID
Compound heterozygous c.680T>C (p.Phe227Ser) and c.2450G>A (p.Arg817His) Homozygous c.2725C > T (p.Pro909Ser)
Homozygous c.2282A > G (p.His761Arg) Homozygous c.2282A > G (p.His761Arg)
5 m
7 m
Birth
Birth
Birth
5m
6 m
Mild cortical NK atrophy (8 m);
8 y Hypotonic quadriplegia
severe cortical atrophy and atrophy and bilateral hyperintensity in the basal ganglia on T2 (21 m)
Diffuse cortical NK atrophy (7 m)
and bedridden (p.Phe227Ser) and c.2450G>A
cataract, nystagmus,deficiency (18 y)
Hearing
loss (13 y)
No
No
corneal opacification Congenital cataract, corneal opacification Congenital cataract
Short stature (-3.5 SD)
No SEMD
No NK
No Cataract No No NK No NK Compound
(5 m)
No (6 m)
Cataract
No
No
NK
No
NK
heterozygous c.607G>C (p.Gly203Arg) and c.2575T>C (p.Phe859Leu) Compound heterozygous
c.2446C>T
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