Table 1.

Selected published SYNE1-associated phenotypes with motor neuron involvement and comparison with the present case

Study	Reported SYNE1 genetic finding(s)	Motor neuron phenotype	Cerebellar / contracture findings	Relevance to present case
Izumi et al. [3]	Patient 1: homozygous c.22456_22457insG, p.R7486fs7488X, together with homozygous c.G553C, p.G185R (source-reported legacy notation; transcript accession not specified in the main article).	Juvenile-onset upper and lower motor neuron involvement preceded cerebellar ataxia by several years and mimicked ALS; respiratory failure developed later.	Cerebellar ataxia and cerebellar/brainstem atrophy appeared later in the disease course; contractures were not reported.	Similar early motor-predominant onset without initial cerebellar involvement; unlike the present case, later cerebellar and severe respiratory involvement occurred.
Synofzik et al. [4]	Twenty-three index patients with biallelic SYNE1 variants (predominantly truncating); motor neuron dysfunction in 15/26 (58%).	Combined upper and lower motor neuron dysfunction in 5/26; isolated upper motor neuron dysfunction in 8/26; isolated lower motor neuron dysfunction in 2/26.	All 26 patients had cerebellar ataxia; 21/26 had ataxia-plus. Scoliosis and pes cavus were reported; Achilles tendon contractures were documented in one patient.	Confirms frequent motor neuron involvement and occasional contractures in biallelic, predominantly truncating SYNE1 disease.
Özoguz et al. [5]	Two Turkish ALS families with autosomal-recessive truncating SYNE1 variants: Q7644X (SYNE#1) and R7842X (SYNE#2); cDNA-level notation was not reported in the source article.	Familial early-onset ALS/MND (onset 20–21 years [SYNE#1] and 17–30 years [SYNE#2]) with spastic-ataxic gait, dysarthria, and dysmetria in both families; oculomotor abnormality additionally reported in Family SYNE#2; fast disease progression noted in Family SYNE#1.	Ataxic/cerebellar features were explicit; cerebellar imaging was not detailed in the source report. Contractures were not reported.	Provides a Turkish comparison with recessive truncating SYNE1-associated MND; the present case adds mild distal finger contractures and 24-month clinical stability.
Nadaf et al. [6]	Homozygous frameshift deletion: chr6:152527389_152527399del; c.22711_22721del; p.(Ala7571ArgfsTer4) (NM_033071).	ALS-like presentation; nerve conduction studies showed preserved sensory responses and upper-limb axonal motor involvement. EMG demonstrated active denervation in the bulbar region and active plus chronic denervation in the cervical, thoracic, and lumbar regions, consistent with clinically definite ALS.	Cerebellar ataxia and severe pancerebellar atrophy were present; contractures were not reported.	Shares motor-predominant neurogenic findings and normal sensory responses, but the present case lacks clinically evident cerebellar involvement.
Naruse et al. [7]	Compound heterozygous SYNE1 variants: c.21,463 C > T, p.(Arg7155Ter), and c.22835_22836delAA, p.(Lys7612SerfsTer28); the transcript accession was not specified in the main article.	Juvenile ALS with upper and lower motor neuron signs, dysarthria, dysphagia, mild limb ataxia, fine hand tremor, pes cavus, cognitive decline, and progressive respiratory impairment; death from respiratory failure at age 39.	Mild limb ataxia and fine hand tremor were present; contractures were not reported.	Represents a complex progressive phenotype; the present case lacks bulbar, cognitive, respiratory, and clinically evident cerebellar involvement and has remained stable over 24 months.
Senghor et al. [8]	Family 1: homozygous NM_182961.4:c.23,131 C > T, p.(Gln7711Ter). Family 2: homozygous splice-site variant NM_182961.4:c.17851-1G > A.	Early-onset MND/juvenile ALS with upper and lower motor neuron signs; progressive weakness, with bulbar and/or respiratory involvement in some affected individuals.	Cerebellar signs were absent or mild; one patient had marked hand contractures and scoliosis, and another developed late mild dysmetria and intention tremor.	Closest MND-predominant/minimal-cerebellar parallel; the reported cases were generally more progressive than the present case.
Present case	Homozygous NM_182961.4:c.21009G > A, p.(Trp7003Ter).	Distal hand atrophy, brisk reflexes, preserved sensory conduction, and widespread chronic neurogenic EMG changes; active denervation most prominent in both abductor pollicis brevis muscles.	No clinically evident cerebellar involvement; mild distal finger contractures; clinically stable over 24 months.	SYNE1-related MND-like phenotype with mild distal contractures. The findings are more consistent with a motor-neuron-predominant SYNE1 phenotype than with an isolated AMC3 phenotype.

ALS amyotrophic lateral sclerosis, AMC3 arthrogryposis multiplex congenita type 3, EMG electromyography, MND motor neuron disease, SYNE1 spectrin repeat containing nuclear envelope protein 1