Clinical Analysis And Literature Review Of A Case Associated With Lower Spinal Muscular Atrophy Caused By Novel Mutation Of DYNC1H1 Gene

Objective: To analyze the clinical features,diagnosis,differential diagnosis,molecular genetics and pathogenicity of DYNC1H1 gene causing spinal muscular atrophy-Lower extremity dominance,to improve pediat rician's knowledge of the disease and various other phenotypes associated with the genetic mutation of the disease and provide assistance for early clinical diagnosis,early supportive treatment and genetic counseling.Methods:The clinical features,laboratory examination,imaging,neuroelectrop hysiology,pathological biopsy and molecular genetics in a child with DYNC1H1 gene mutation were analyzed in detail.Results:The patient,a 9-year-old girl,was treated for walking instability.After the child began to walk independently 8 years ago(1 year old),the family members found that the child walked unstable,presented a waddling gait and was prone to fall down.Six years ago,the family members found that the child could not go upstairs alone,could not squat up alone,could not run,could not complete jumping movements.Six months ago,family members found that children with Hypoalgesia,weakness and thinning of the lower extremities,cotton feeling,the current unstable walking than progressive aggravation,frequent falls.Main ex amination: High Arch Feet,waddle Gait,hypertrophy heel and lateral margin of foot,slender both lower limbs,proximal lower limbs muscle strength V-grade,both upper limbs normal muscle strength,normal limb muscle tension.Bilateral positive finger-nose test,clumsy alternate test.Hypoalgesia below the level of 2-3 on the left side and 5-6 on the right side of the neck.Hypoesthesia in the right joint.Bilateral Radial periosteum reflex disappeared,bilateral tendon reflex disappeared,bilateral tendo n reflex disappeared,bilateral metatarsal reflex disappeared,bilateral Hoffmann's sign negative,bilateral Babinskin sign did not emerge,kirschner sign negative.The abnormal signals in the right Basal Ganglia region were observed by MRI examination after admission.Magnetic resonance imaging(MRI)of the spinal cord showed secondary central Canal dilation after atrophy.EMG showed chronic myogenic damage to bilateral anterior tibialis,bilateral quadriceps FEMORIS,bilateral gastrocnemius and left rectus abdominis.A biopsy of the left quadriceps muscle revealed neurogenic damage.Genetic TESTING: heterozygous mutation was found in DYNC1H1 from the mother.A heterozygous mutation into C.751 C & GT;T(The coding region of Nucleotide No.751 is changed from cytosine to thymine),resulting in a change in the amino acid p.R251C(Arg 251 mutated to Cysteine)is a missense mutation(table 1).Family History: The affected child's mother appeared in early childhood unstable walking,waddling Gait,now can see high arch foot,can walk independently,still for waddling gait,but can not stand up independently,did not involve upper limbs,no intellectual disability.The final diagnosis was DYNC1H1 gene mutation-induced severe spinalmuscular atroph y of the lower extremities.Conclusion:1.Dync1h1 gene mutation induced significant cristae muscular atrophy of the lower extremity belongs to neurologic genetic disorder,which is characterized by progressive weakness of the proximal muscles of the lower extremity and degeneration of the motor neurons of the anterior Horn of the spinal cord,it has significant clinical and genetic heterogeneity.2.Dync1h1 gene mutation-induced significant CRISTAE muscular at rophy of lower limbs has a certain phenotype-gene correlation.3.The key to the diagnosis of DYNC1H1 gene mutation-induced severecristae muscular atrophy of the lower extremities is to improve the relevant historical data,assist examination,and exclude other causes that can cause the appearance of associated phenotype at the same time,charcot-marie-tooth(CMT),autosomal dominant mental retardation type 13 and other diseases have similar clinical phenotypes.4.Dync1h1 gene mutation-induced severe cristae muscular atrophy of lower extremity is a genetic disease without effective treatment,mainly symptomatic support and prevention the disease.