Table 1.

Clinical description of patients carrying homozygous ADPRHL2 missense variants showing variable phenotypes.

Individual	A:II:1 (patient 1)	A:II:2 (patient 2)	B:II:1 (patient 3)
Gender	M	M	F
Parental consanguinity	Reported negative	Reported negative	+
Current age or age at death	34 yr	32 yra	16 yra
Circumstances of death	—	Cardiac arrest/respiratory failure	Respiratory failure
ADPRHL2 Mutation
Genomic position (hg19)	Chr1: 36558899T>G	Chr1: 36558899T>G	Chr1: 36554582G>T
cDNA	NM_017825: c.1004T>G	NM_017825: c.1004T>G	NM_017825: c.77G>T
Protein	p.Val335Gly	p.Val335Gly	p.Cys26Phe
Clinical features
Age at onset	13 yr	15 yr	15 mo
Symptoms at onset	Walking instability and intermittent lateropulsion	Fatigue and instability during walking	Febrile seizures
Psychomotor development	Normal	Normal	Normal speech, moderate intellectual disability (6 yr)
General development	Normal	Normal	Growth retardation for which growth hormones were supplied
Gait	Weakness of foot dorsiflexors, drop foot, and mild spasticity	Foot dorsiflexor weakness, drop foot, mild spasticity, and instability; later also affected by fracture	Weakness of foot dorsiflexors, drop foot
Muscle atrophy	Moderate atrophy of distal third of upper and lower limbs	Moderate atrophy of distal upper and lower limbs and mild proximal atrophy	Moderate atrophy of intrinsic hand muscles (10 yr), mild atrophy of distal lower limbs
Proximal strength upper limb	5	5	5
Distal strength upper limb	4	2–4	2/5 to 4-/5
Proximal strength lower limb	5	5	5
Distal strength lower limb	1–2	1–3	4-/5 to 5/5
Reflexes upper limb	Normal	Diminished	Normal
Reflexes lower limb	Normal	Distally diminished	Normal
Sensory involvement	Hypoesthesia in tip toes, deep position, and vibration sense severely diminished in lower legs and hands	Hypoesthesia and loss of vibration sense in legs	-
Seizure type	-	Myoclonic jerks	Febrile seizures
Cardiac features	Normal	Normal	Left ventricle hypertrophy and mitral insufficiency
Other clinical features	Motor tics in childhood, micrognathia, nystagmus, postural tremor, absent trunk hair, pes cavus, mild to moderately restrictive pulmonary function, and scoliosis	Nystagmus, postural tremor, mild dysarthria, pes cavus, hyperhidrosis, absent trunk hair, carpal tunnel surgery, and mixed restrictive/obstructive lung function	Moderate scoliosis, growth retardation, pes cavus, and exostosis with confirmed causal EXT1 variant
Neurological examination
EMG	Severe axonal motor polyneuropathy and mild sensory involvement	Severe axonal motor polyneuropathy and mild sensory involvement	Profound axonal motor polyneuropathy, no sensory involvement
Brain MRI (age performed)	Normal (13 yr)	Normal (26 yr)	Normal (13 yr)
	Mild white matter hyperintensity lesions (33 yr)
EEG	Normal	Mild nonspecific changes with intermittent bifrontal theta waves	Sporadic epileptiform activity frontocentral localization
Other genetic features	-	-	NM_000127.2 (EXT1): c.538_539delAG (p.Leu181Profs)

^aIndividual is deceased