P3.N263: Kugulberg Walender Syndrome, Spinal Muscular Atrophy SMA Type 3, A Diagnostic Challenge

Introduction: Spinal Muscular Atrophy is a heterogeneous disorder caused by homozygous deletion of survival motor neuron 1(SMN1) gene on chromosome 5q13. It is a progressive disease with four types based on timings of onset of the clinical features. We present a six-year-old boy who had weakness of lower limbs for the last 4 years and diagnosis was delayed due to unusual presentation and rarity of this SMA type 3 in our population.

Case Description: A six-year-old boy brought with a history of progressive weakness of lower limbs for last four years. He was asymptomatic till two years of age after which he started having weakness of both lower limbs. His walking problem has gotten worse over time.

He was born by an uneventful delivery to a consanguineous parent. His elder siblings are alive and healthy. He achieved all gross and fine motor developmental milestones at an appropriate age. He has normal speech and is a student of class 1. Examination revealed an overweight, alert intelligent looking boy with weight of 28 kg and FOC 50 cm. lower limb examination shows normal bulk, tone slightly reduced with a power of 4/5 in both limbs. Deep tendon reflexes were reduced bilaterally. His Gower sign was positive with a lordotic gait. Upper limbs had normal bulk, tone, reflexes, and power. His Higher mental functions, cranial nerves, sensory and cerebellar examination was normal. The rest of the systemic examination was unremarkable.
He worked up on the line of Duchenne muscular dystrophy previously at 03 years of age with CPK of 356. Muscle biopsy revealed increased endomysial fibrosis and fatty replacement of muscles. EMG of brachioradialis showed low amplitude motor action potentials and reduce recruitment suggesting myopathy. Nerve conduction study was normal. MRI brain was unremarkable. No deletion or duplication for dystrophin gene was identified on PCR.
Keeping in view of normal Dystrophin gene and no signs of myopathy, the case was thoroughly reevaluated and PCR for SMN gene was advised. Homozygous deletion in SMN1 gene was detected and 3 copies of SMN 2 genes were present. The patient was finally diagnosed as case of SMA type 3A.

Discussion: SMA Type 3, Kugulberg-Walender syndrome is a rare disorder in our population. It was a diagnostic dilemma as our patient did not have tongue fasciculations, tremors on outstretched hands, and was a healthy toddler without any muscle atrophy. Since there was progressive weakness of proximal muscles with positive Gower sign and normal dystrophin gene, SMN gene was advised which revealed homozygous deletion of SMN1 gene and 3 copies of SMN2 gene.

Conclusion: Timely diagnosis with multidisciplinary and new advances in treatment is the key to the normal life expectancy in a patient with SMA type 3