Table 3.

Phenotypes of index patients with genetic variants

Gene	Amino acid change	Origin	AAO (year)	Inheritance	Sensory involvement	Motor involvement	Reflexes	Ulceromutilating complications	Autonomic symptoms	NCS	Other features	References
SPTLC1 family 1	p.Ala310Glyba,b	UK	50s	U	Pin prick absent throughout, vibration reduced to costal margins Sensory ataxia	None	Present	5th digits of both feet amputated	No	Sensory axonal neuropathy
SPTLC1 family 2	p.Cys133Trp	UK	20	AD	Pinprick reduced to forearm and knee, vibration to ankles	Distal UL and LL weakness	Absent in LL	Ulcers on feet	No	Sensory motor axonal neuropathy		[9]
SPTLC1 family 3	p.Cys133Trp	UK	29	AD	Sensory loss in feet	None	All reduced	None	No	Sensory motor axonal neuropathy	Lancinating pain	[9]
SPTLC1 family 4	p.Cys133Trp	UK	24	AD	Pinprick reduced above elbows and thighs, vibration to hips	Severe distal UL and LL weakness Hand contractures, Wheelchair	Absent in LL	Osteomyelitis	No	Sensory motor demyelinating neuropathy	Lancinating pain	[9]
SPTLC1 family 5	p.Cys133Trp	UK	16	AD	Pinprick reduced in hands and feet	Distal UL and LL hand	Absent at ankle	Ulcers on feet	No	Sensory motor axonal neuropathy		[9]
SPTLC1family 6	p.Cys133Trp	UK	20	AD	Pinprick reduced to wrists and thighs, vibration to ankle	Distal weakness UL and LL	Absent at ankle	Ulcers on hands and feet, fingers amputated	No	Sensory motor axonal neuropathy	Lancinating pain	[9]
SPTLC1family 7	p.Cys133Trp	UK	18	AD	Sensory loss in UL and LL	Sever UL and LL weakness	Absent	Ulcers on feet, toes amputated	No	Sensory motor axonal neuropathy	Lancinating pain	[9]
SPTLC1 family 8	p.Cys133Trp	UK	60	AD	Pinprick reduced above elbows and mid thigh, vibration to costal margin	Severe distal UL and LL weakness Wheelchair	Absent in LL	Ulcers on feet	No	Sensory motor demyelinating neuropathy	Lancinating pain	[9]
SPTLC1 family 9	p.Cys133Trp	UK	18	AD	Pinprick reduced above elbows and upper thighs, vibration to hips	Severe distal wasting and weakness UL and LL	Absent in LL	Ulcers on feet	No	Sensory motor axonal neuropathy	Lancinating pain	[9]
SPTLC1 family 10	p.Cys133Trp	UK	Teens	AD	Sensation reduced in feet	Presentc	–	Trophic changes in fingers	No	Sensory motor demyelinating neuropathy
SPTLC1 family 11	p.Cys133Trp	UK	Teens	AD	Presentc	Presentc	–	Trophic changes in fingers	Mild bladder and bowel disturbances	N/A	Lancinating pain
SPTLC1 family 12	p.Cys133Trp	UK	–	AD	Presentc	–	–	–	–	N/A
SPTLC1 family 13	p.Cys133Trp	UK	18	U	Pinprick reduced to elbows and knees, vibration to ankle	Distal weakness and wasting UL and LL	Absent in LL	Ulcers in lower legs and eye bulb	Mild bowel disturbances	Sensory motor axonal neuropathy	Lancinating pain
RAB7 family 14	p.Asn161Thr	UK	16	AD	Pinprick reduced to ankles, vibration to costal margin	None	Absent at ankles	Scoliosis amputation middle left toe, deformity left foot	No	Sensory motor neuropathy		[10]
HSN2 family 15	p.[Cys20TrpfsX18] + [Thr390CysfsX21]a	Malta	Congenital	AR	CIP	No	–	Ulcers un noticed fractures osteomecrosis of ankle	No	Sensory motor axonal neuropathy
HSN2 family 16	p.[Thr390CysfsX21] + [Thr390CysfsX21]a	Malta	Congenital	AR	CIP	No	–	Ulcerations, Finger tips amputated due to repeated trauma	–	N/A
FAM134B family 17	p.[Gln145X(+) Gln145X]	Somalia	5	AR	Glove and stocking loss to pin	Significant weakness requiring wheelchair	Absent/diminished	Ulcers, right forefoot amputation scoliosis, ankle deformity acro-osteolysis of finger and toes	No	Sensory motor axonal neuropathy		[18]
FAM134B family 18	p.[Gly216Arg(+) Gly216Arg]a,b		10	AR	Pin prick reduced in toes	No	Diminished at ankles	Ulcerations, pes cavas scoliosis	No	Sensory axonal neuropathy
NTRK1 family 19	p.[Gln176X] + [Gln176X]	Saudi Arabia	1st month	AR	CIP	No	Normal	Osteomyelitis, injury to lips and tongue	Anhidrosis bouts of fever	N/A	Cognitive delay
NTRK1 family 20	p.[Try359X] + [Try359X]	Saudi Arabia	Birth	AR	CIP	No (wheelchair bound due to osteomylitis resulting in deformities of feet)	Normal	Charcot joint knee, osteomylitis, injury to lips and tongue	Anhidrosis bouts of fever	Sensory axonal neuropathy
NTRK1 family 21	p.[Arg654Cys] + [Arg654Cys]	Saudi Arabia	Birth	AR	CIP	No	Normal	Injury to lips and tongue	Anhidrosis bouts of fever	Sensory axonal neuropathy	Cognitive delay
NTRK1 family 22	p.[Glu492Lys] + [Glu492Lys]a	UK/USA	Congenital	AR	CIP	Delayed motor milestones	Absent/diminished	Multiple injuries and burns on hands	Anhidrosis bouts of fever	Sensory axonal neuropathy	Deafness, cognitive delay
NTRK1 family 23	p.[Arg6Trp(+)Arg6Trp]a,b	UK	Adult	AD	Yes	No	–	No	No	N/A	Dementia, deafness
NGFB family 24	p.Gly161_Glu162dupa,b	UK	48	AD	Glove and stocking loss to pin. vibration reduced to costal margins	No	Absent ankle reflexes	Charcot joints in both ankles, deformities in both knees	No	Sensory motor axonal neuropathy
NGFB family 25	p.Ser187Asna,b	Ireland	Congenital	Sporadic	CIP	–	–	–	–	N/A

AAO Age at onset, AD autosomal dominant, AR autosomal recessive, CIP congenital insensitivity to pain, U unknown, N/A not available, UL upper limbs, LL lower limbs

^aNovel

^bUncertain significance

^cLimited details available