Table 1.

Clinical features of patients with homozygous p. Arg109Ter variant

Family	Family A		Family B		Family C	Family D	Family E
	A-II-1	A-II-2	B-II-1	B-II-2	C-II-1	D-II-1	E-II-1
Ethnicity	South Italian	South Italian	Saudis/Yemenis	Saudis/Yemenis	Turkish	Tunisian	Tunisian
Sex	M	F	M	M	M	F	F
Age at last follow up	Died at 6 y	34th wk of gestation	6 y	2 mo	8 mo	Died at 10 d	Died 24 h after birth
IUGR	+	+	–	–	–	+	–
Gestational age at birth, wk	41	n/a	34	34	38	38	40
Head circumference, (at birth and follow up)	32 cm, 38 cm at 3y	n/a	29 cm, 34 cm at 2y	30.5 cm, 31.5 at 2 mo	n/a	n/a	n/a
Respiratory failure at birth	+	n/a	+	+	+	+	+
Tone	Axial hypotonia, appendicular hypertonia	n/a	Hypotonia	Hypotonia	Axial hypotonia, lower limb hypertonia	Axial hypotonia, lower limb hypertonia	Appendicular hypertonia
Global developmental delay	+	n/a	+	n/a	+	n/a	n/a
Seizures, type, onset	Yes, myoclonic, neonatal onset	n/a	Yes, myoclonic, neonatal onset	n/a	Yes, myoclonic, neonatal onset	n/a	Yes, myoclonic, neonatal onset
EEG (initial and follow up)	Slow cortical activity	n/a	Low amplitude, attenuated background of mixed delta theta	Low amplitude, attenuated background of mixed delta theta	Slow activity, diffuse arrhythmia, multifocal epileptic disorders	Areactive, discontinuous tracing, burst suppression pattern	n/a
Movement disorder	+	n/a	–	+	+	+	Trismus
	Exaggerated startle responses triggered by tactile stimulations, chewing movements			Exaggerated startle responses triggered by tactile stimulations	Exaggerated startle responses triggered by tactile stimulations	Fasciculation and tremors
Brain MRI abnormalities	Progressive global atrophy involving the cerebral and cerebellar hemispheres, cerebral dysgyria, immature white matter, conspicuous basal ganglia degeneration	Progressive atrophy with particular cerebellar atrophy and dysgyria due to immature cortical folding	Global underdevelopment of the brain with cerebral dysgyria, particular cerebellar hypoplasia and atrophy	Cortical dysgyria, cerebellar atrophy, inferior cerebellar vermis hypoplasia, global cerebral underdevelopment with white-matter immaturity	Parenchymal atrophy with immature white matter	Supratentorial atrophy, cortical dysgyria, diffuse white matter immaturity	Cortical atrophy
Ophthalmological findings	Bilateral congenital cataract	n/a	Nystagmus	–	Nystagmus, strabismus	n/a	n/a
Bilateral hearing loss	+	n/a	+	+	n/a	n/a	n/a
Dysmorphic features	Triangular face, frontal bossing, occipital flattening	n/a	Triangular face, frontal bossing, up-slanting palpebral fissures, bulbous nasal tip	Triangular face, frontal bossing, up-slanting palpebral fissures, bulbous nasal tip	n/a	n/a	–
Limb contractures	+	n/a	+	+	+ (Distal)	n/a	+
Cardiorespiratory problems	Tachycardia, incomplete RBBB, respiratory failure	n/a	PDA (closed) and ASD, respiratory failure, bronchomalacia of right upper lobe bronchus	ASD (small), respiratory failure	Patent foramen ovale, respiratory failure	–	Severe pulmonary hypertension
Other findings and abnormalities	–	n/a	Bilateral undescended testicles, mild dilatation of the pelvis of the right kidney	Bilateral undescended testicles, mild hydronephrosis on the right side	Undescended testis	–	Thymus hyperplasia

ASD, autism spectrum disorder; EEG, electroencephalogram; F, female; IUGR, intrauterine growth restriction; M, male; MRI, magnetic resonance imaging; n/a, not available or not applicable; PDA, patent ductus arteriosus; RBBB, right bundle branch block.