Missense mutation in DYNC1H1 gene caused psychomotor developmental delay and muscle weakness: A case report

Table 1 Clinical features of gene mutation patients with DYNC1H1 gene mutation

Patient	Age (yr)	Sex	Main clinical manifestations	Mutation	Ref.
A four-generation family with 23 members affected	-	-	Pes cavus at birth; delayed motor milestones; lower limb weakness; speech delay; learning difficulties	Heterozygous; c.917A>G, p.His306Arg	[9]
I 2	82	Female	Lower limb muscle wasting and weakness; walked with a waddling gait	Heterozygous; c.1809A>T, p.glu603Asp	[11]
II 1	60	Male	Lower limb muscle wasting and weakness; had learning difficulties and epilepsy
II 2	59	Male	Bilateral talipes equinovarus, congenital hip dislocation, and scoliosis; lower limb weakness and difficulty walking
II 3	58	Male	Bilateral talipes equinovarus and congenital hip dislocation requiring surgeries; bilateral pes cavus, wasting of muscles (particularly quadriceps), reduced reflexes, but normal sensation in the lower limbs and walked very slowly with a waddling gait
III 1	32	Male	Similar features as #II 3
III 2	30	Male	Similar features as #II 3
Patient 1	15	Female	Middle East. Twenty months: Delayed walking and early predominant weakness in the lower extremities. Investigations showed normal creatine kinase levels and nerve conduction study findings, and needle electromyography suggested neuronal degeneration. Brain MRI: Mild ventricular dilatation. Muscle biopsy from right vastus lateralis: Neurogenic atrophy with pathological fibre-type grouping and fatty infiltration in the muscle fascicles. At 15 yr old, walked independently with waddling and needed support to rise from floor. Longer distance travel: Wheelchair. At present, mild proximal upper limbs weakness; mild intellectual disabilities	De novo heterozygous; c.751C>T, p.Arg251Cys	[12]
Patient 2	16	Female	Chinese. At birth: Clubfeet; 2 years old: Delayed walking; 7 years old: Pes cavus, significant lower limb muscle wasting and weakness, absent knee jerks but preserved ankle jerks, positive Gower sign, mild proximal muscle weakness in the upper extremities with preserved reflexes. Mildly elevated creatine kinase level (255 U/L, normal reference: < 154 U/L). Muscle biopsy from the right deltoid: Type 2 fibre atrophy. Needle electromyography: Chronic denervation. 12 years old: Mild scoliosis with Cobb’s angle of 14 degrees from T12 to L5. Attention deficit and hyperactivity disorder with dyslexia. 14 years old: Walk independently but required to use a walking stick for long distance travel. Leg muscle MRI: Selective muscle involvement and no deterioration when repeated 1.5 yr later. 18 years old: Knee tightness increase; scoliosis and motor performance stable. Brain MRI: Mild ventricular dilatation
Patient 3	8	Male	Chinese. At birth: Club feet. 2 years old: Started walking and fell easily. Normal to mildly elevated creatine kinase levels (CK148 - 216 IU/L: normal reference: < 163 IU/L). Muscle biopsy from left quadriceps reported predominant type 1 fibres with rare scattered atrophic fibres. Brain MRI: Mildly dilated lateral ventricles and a left posterior fossa arachnoid cyst. 7 years old: Positive Gower sign and predominant lower limbs weakness and atrophy with absent knee jerks and decreased ankle jerks. Mild shoulder girdle weakness with preserved reflexes. Needle electromyography: Chronic denervation. 8 years old: Selective muscles involvement. 11 years old: Attention deficit disorder and motor performance remained stable with knee and tendoachilles tightness
Patient 4	21	Male	Caucasian. At birth: Left clubfoot. 27 mo old: Walked led by hand. Right quadricep muscle biopsy: Predominant type 1 fibres surrounded by fat and fibrosis. Needle electromyography: Neurogenic pattern. Urinary and faecal incontinence problem. 6 years old: Predominant weakness and atrophy of both legs, more pronounced on the left side. His knee jerks were absent but the ankle jerks were preserved. He could walk up to a 100-m distance. 8 years old: Muscle ultrasound: Abnormal echogenicity of the quadriceps and bicep brachii. Mild grade intellectual disabilities and autism with hyperactive behaviour. Over the next few years: Lower limb weakness increased and upper extremities proximal weakness. Twelve years old: Walk with walking stick. 21 years old: Walk up to several meters and required a wheelchair for long distance travel. Pronounced muscle atrophy of the legs and marked contractures at both knees. Repeated brain MRI: Small right-sided posterior fossa arachnoid cyst
Family 10	4	Male	Parental nonconsanguinity; Seizure onset; 3 mo: Focaltonic/opisthotonic posturing. IS (6 mo) to multiple types. EEG: MEA + AB, Severe DD, ASD, focal pachygyria	Heterozygous; c.5884C>T, p.Arg1962Cys	[15]
Case 4	7	Female	Prenatally believed to have isolated mild ventriculomegaly but with additional postnatal findings; ventricular width: 12.0 mm; MRI: Sinuous malformation; intellectual disability, impaired psychomotor development; follow-up sonograms: Regression to normal	Heterozygous; c.5884c>T; p.Arg1962Cys	[16]

IS: Infantile spasms; EEG: Electroencephalogram; ASD: Autism spectrum disorder; AB: Abnormal background; DD: Developmental delay; MEA: Multi-electrode arrays; MRI: Magnetic resonance imaging.