Table 2.

Detail clinical information, prior investigation findings, WES result and diagnosis of the 13 patients with positive findings in this cohort

Project No.	Sex/ Age	Onset	NMD sub group	Motor	Clinical presentation	Systemic involvement (respiratory, cardiac, cognition, musculoskeletal)	Investigations						WES findings		ACMG CLN Post_P value by Bayesian calculation	Reported/ Novel (diagnosis)
							MRI brain	MRI muscles	CK U/L	Muscle biopsy	NCS & EMG	Prior normal gene studies
NMD 006	F/18	B	CM	Delayed walking since 24 months	Arthrogyposis multiplex congenita and delay walking, followed by stabilization of motor performance since then. Exam showed facial, neck flexor and limb girdle weakness, pectus excavatum, rigid spine, and club feet.	Respiratory: Restrictive lung function Cardiac: Mitral valve prolapse and regurgitation with left ventricular dilatation on Lisinopril Cognition: Normal Musculoskeletal: rigid spine, pes cavus	NAD	ABN	54–200	Nonspecific myopathic change	NCV: Absent bilateral peroneal CMAP responses EMG: Myopathic	—	ACTA1 (NM_001100.3)	c.874A>G, p.(Arg292Gly) de novo	Likely pathogenic (0.975)	Novel (Congenital myopathy)
NMD 037	F/1 month	AN	CM	Non‐ambulatory Minimal active movement	Antenatal polyhydramnios and decrease fetal movement. Born prematurely at 32 weeks of gestation, required intubation, and resuscitation at birth. Exam showed generalized weakness with poor respiratory effort. Developed chylothorax required chest drain. Died at 46 days old.	Respiratory: Intubated and ventilated since birth Cardiac: Normal Cognition: Uncertain Musculoskeletal: Bilateral shoulder, wrist, finger, knee, ankle contractures	ND	ND	298	ND	ND	SMN1	ACTA1 (NM_001100.3)	c.1001C>G, p.(Pro334Arg) de novo	Likely pathogenic (0.975)	Reported (Laing et al., 2009) Nemaline myopathy (Congenital myopathy)
NMD 033	M/22	B	CM	Walking before 18 months Fell easily at early age Lost ambulation at 13 years	Neonatal‐onset hypotonia and mild generalized weakness. Independent walking at a young age with waddling and easy falling. Lost ambulation at 13 years and required nocturnal NIV since aged 14 and continuous use since aged 19. Developed progressive scoliosis, and lost ability to sit at aged 22. Exam revealed facial weakness with ptosis, ophthalmoplegia, generalized weakness, muscle wasting, marked scoliosis.	Respiratory: Nocturnal NIV since 14 years; Continuous NIV since 19 years Cardiac: Normal Cognition: Normal Musculoskeletal: Cavovarus feet with surgeries; Scoliosis with initial brace use; refused scoliosis surgery	ND	ND	21–72	congenital fiber‐type dispropor‐tion	Refused	—	DNM2 (NM_001005360.2)	c.1852G>A, p.(Ala618Thr) de novo	Likely pathogenic (0.975)	Reported (Bitoun et al., 2007) Centronuclear myopathy (Congenital myopathy)
NMD 016	M/16	CH	CM	Delayed walking since 21 months	Delayed walking and persistent motor clumsiness with increased walking difficulty at 10 years. Developed type II respiratory failure required BIPAP at 13 years. Rigid spine with neck hyperextension observed at 14.5 years. Exam showed limb girdle weakness (lower limb > upper limb) and contractures.	Respiratory: Nocturnal NIV since 13 years Cardiac: Normal Cognition: Normal Musculoskeletal: Progressive rigid spine, contractures at shoulders, elbows, ankles	NAD	ABN	↑ 116–360	Nonspecific myopathic change	NCV: Small CMAPs EMG: ND		SELENON (NM_206926.1)	c.238delG, p.(Asp80Thrfs*20) unknown inheritance c.1304G>A, p.(Arg435Gln) maternal inherited	Likely pathogenic and VUS (0.994 and 0.900)	Novel (Rigid spine syndrome)
NMD 046	F/19	IN	MD	Delayed walking since 18 months	Noted hypotonia & dislocated hip in first year of life. Delayed walking at 18 months old. Required orthopaedic intervention to both hip dislocation at aged 2. Persistent waddling gait and failed to climb stairs unassisted at 6 years of age. Exam revealed facial rash, pilaris keratosis, distal hyperlaxity, marked limb girdle weakness, elbow, and finger flexor contracture, marked equinovarus.	Respiratory: No need for ventilator Cardiac: Normal Cognition: Normal Musculoskeletal: Dislocated hip before 1 years; progressive long finger flexor, elbow flexor and knee flexion contractures, tight Achilles tendons; scoliosis without brace	NAD	ND	61–299	Dystrophic change, severe deletion of collagen VI in sarcolemma	NCV: Normal EMG: Myopathic	—	COL6A1 (NM_001848.3)	c.850G>A, p.(Gly284Arg) de novo	Pathogenic (1.000)	Reported (Giusti et al., 2005) Ullrich CMD (Ullrich CMD)
NMD 008	M/18	CH	MD	Walking since 12 months	Normal walking at 1 years old, but persistent easy falling and motor clumsiness after 6 years. Examination revealed mild limb girdle weakness (lower limb > upper limb), distal hyperlaxity. Facial rash, follicular hyperkeratosis, contractures over finger flexors, elbows, and tendoachilles, pes cavus.	Respiratory: Mild obstructive sleep apnea syndrome Cardiac: Normal Cognition: Normal Musculoskeletal: Progressive long finger flexor, elbow flexion and knee flexion contractures, tight Achilles tendons	NAD	ABN	↑ 299–1,311	Dystrophic changes ↓ alpha‐dystrogly‐can no collagen VI staining done	NCV: Normal EMG: Myopathic	DMD FKTN FKRP	COL6A1 (NM_001848.3)	c.1056 + 2dupT de novo	Pathogenic (1.000)	Novel (Bethlam myopathy)
NMD 013	M/8	CH	MD	Walking since 12 months	History of persistent clumsiness since walking began. Noted lower limb weakness at 2 years. Exam showed thin body build, limb girdle weakness (lower limb > upper limb), elbow & finger contractures, and tight tendoachilles.	Respiratory: Normal Cardiac: Normal Cognition: Normal Musculoskeletal: Contractures at elbows and ankles	NAD	ABN	↑ 699–1,259	Myopathic change Core‐like structures	NCV: Normal EMG: Myopathic	SElENON	LMNA (NM_170707.4)	c.1357C>T, p.(Arg453Trp) de novo	Likely pathogenic (0.999)	Reported (Bonne et al., 1999) EDMD (EDMD)
NMD 048	F/1	NN	MD	Sitting Walking with support	Noted hypotonia, hyporeflexia, significant head lag and decreased active limb movement in the first month of life. Persistent gross motor delay. Sat unsupported at 9 months.	Respiratory: Normal Cardiac: Normal Cognition: Normal Musculoskeletal: No contractures	ABN	ND	↑ 2,253–2,887	ND	NCV: Small CMAPs EMG: ND	—	LAMA2 (NM_000426.3)	c.250C>T, p.(Arg84*) unknown inheritance c.4157A>T, p.(Tyr1386Phe) unknown inheritance	Likely pathogenic and VUS 0.994 and 0.325	Novel (Merosin deficient CMD)
NMD 007	F/12	CH	MD	Walking since 16 months	History of developmental delays & mild joint laxity. Asymptomatic hyperCKaemia with no clinical weakness. Microcephaly. Mild autism spectrum disorder.	Respiratory: Normal Cardiac: Normal Cognition: Mild intellectual disabilities, autism spectrum disorder Musculoskeletal: Normal	NAD	AB	↑1408–3,883	ND	Both NCV and EMG normal	DMD	POMT1 (NM_007171.3)	c.685C>T, p.(Gln229*) maternally inherited c.1024C>T, p.(His342Tyr) paternally inherited	Likely pathogenic and VUS (0.997 and 0.812)	Novel (Asymptomatic HyperCKaemia)
NMD 010	F/33	CH	PN	Walking since normal age Independent walking until 17 years	History of easy falling and foot deformity requiring orthopedic surgeries during childhood. Progressive weakness with loss of ambulation at 17 years, nocturnal NIV since 29 years. Exam revealed ptosis, facial weakness, soft & hoarse voice, generalized limb weakness (distal > proximal), muscle wasting in hands, and calves.	Respiratory: Nocturnal NIV since 29 years Cardiac: Normal Cognition: Normal Musculoskeletal: Contractures at fingers, knees and ankles, mild scoliosis	ND	ND	30–91	End stage changes suspected decrease collagen VI	NCV: Refused initially, agreed after genetic result available – no SNAP, CMAP responses EMG: ND	COL6A1, COL6A2, COL6A3	MTMR2 (NM_016156.5)	c.1797_1798insAGAA, p.(Leu600fs*5) maternal inherited c.1387−2A>G unknown inheritance	Pathogenic (0.994 and 0.994)	Novel (CMT 4B1)
NMD 060	F/7	CH	PN	Walking since 15 months Independent walking	History of easy falling and unsteady gait since walking began. Exam showed mild proximal girdle weakness but significant distal weakness with muscle wasting and mild tightness in Achilles tendons.	Respiratory: Normal Cardiac: Normal Cognition: Unknown Musculoskeletal: Normal	ND	ND	83	ND	NCV: SM axonal polyneuro‐pathy EMG: Neurogenic	—	IGHMBP2 (NM_002180.2)	c.1060G>A, p.(Gly354Ser) paternally inherited c.2356delG, p.(Arg786fs*45) unknown inheritance	Likely pathogenic (0.900 and 0.994)	Reported (Giannini et al., 2006; Liu et al., 2017) SMARD type I (CMT 2)
NMD 042	M/14	CH	PN	Normal walking age Independent walking	History of intermittent lower limb pain and motor clumsiness since 8 years. Stable motor performance with mild progressive distal muscle weakness, especially weak ankle dorsiflexors with varus deformity of the feet over time.	Respiratory: Normal Cardiac: Normal Cognition: Normal Musculoskeletal: Contractures at ankles	ND	ND	48–127	ND	NCV: SM demyelina‐ting polneuro‐pathy EMG: ND	PMP22	MPZ (NM_000530.8)	c.737A>G, p.(Asp246Gly) de novo	Likely pathogenic (0.975)	Novel (CMT1B)
NMD 034	F/8	CH	CN	Walking since 12 months	Walked at a normal age but had persistent easy falling and motor clumsiness after 2 years. Very mild lower limb girdle weakness noted on examination.	Respiratory: Normal Cardiac: Normal Cognition: Normal Musculoskeletal: Skeletal dysplasia	NAD	NAD	100	ND	NCV: Normal EMG: neurogenic	SMN1	TGFB1 (NM_000660.6)	c.653G>A, p.(Arg218His) de novo	Likely pathogenic (0.975)	Reported (Kinoshita et al., 2000) Camurati‐Engelmann disease (Camurati‐Engelmann disease)

Abbreviations: ↑, increased; ABN, abnormal; ACMG CLN, American College of Medical Genetics and Genomics Classification; AD, adulthood; Adol, adolescence; AN, antenatal; B, birth; BIPAP, Bilevel positive airway pressure; BMD, Becker muscular dystrophy; CH, childhood; CK, creatine kinase; CM, hereditary congenital myopathy subgroup; CMAP, compound muscle action potentials; CMD, Congenital muscular dystrophy; CN, complex condition with neuromuscular involvement subgroup; EDMD, Emery Dreifuss muscular dystrophy; EMG, electromyography; F, female; IN, infantile; LGMD, limb‐girdle muscular dystrophy; M, male; MD, hereditary muscular dystrophy subgroup; MRI, magnetic resonance imaging; NAD, normal; NCS, nerve conduction study; NCV, nerve conduction study; ND, not done; NIV, noninvasive ventilation; NMDs, Neuromuscular disorders; NN, neonatal; PN, hereditary peripheral neuropathy subgroup; SM, sensorimotor; SMARD, spinal muscular atrophy with respiratory distress; SNAP, sensory nerve action potentials; VUS, variant of unknown sequencing; WES, whole‐exome sequencing.