Genetic testing for SYNE1 is available. Testing is considered supportive for diagnosis.

System/Concern | Evaluation | Comment

Neurologic

| Assessment by neurologist for:

• Cerebellar motor dysfunction (gait postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades smooth pursuit)

• UMN /or LMN dysfunction (weakness, spasticity, Babinski signs, hyperrefflexia, amyotrophy, fasciculations)

• Vibration loss or polyneuropathy based on clinical findings

| • Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS).1

• Consider electrophysiologic studies (EMG NCS) to detect neurogenic changes or signs of neuropathy.

• Brain MRI to evaluate presence severity of cerebellar atrophy

Refer to neuromuscular clinic (OT/PT/rehabilitation specialist). | To assess gross motor fine motor skills, ambulation, need for adaptive devices PT

Speech

| For those w/dysarthria: speech/language evaluation |

Feeding

| For those w/frequent choking or severe dysphagia, assess:

• Nutritional status

• Aspiration risk

| Consider involving a gastroenterology/nutrition/feeding team.

Respiratory

| For those w/respiratory symptoms or muscular involvement: obtain pulmonary function tests | Consider involving ...

Source: GeneReviews — "SYNE1 Deficiency"

• Monitor ataxia progression w/standardized scale (SARA, ICARS, or BARS)1

| Annually; more often for an acute exacerbation

Physiatry, OT/PT assessment of mobility, self-help skills as they relate to ataxia, spasticity, weakness

Dysarthria

| Need for alternative communication method or speech therapy | Per symptom progression

Dysphagia

| Assess aspiration risk feeding methods

Cognitive/

Psychiatric

| Evaluate mood, signs of psychosis, cognitive complaints to identify need for pharmacologic psychotherapeutic interventions. | Per symptom progression development of psychiatric symptoms

BARS = Brief Ataxia Rating Scale; ICARS = International Co-operative Ataxia Rating Scale; LMN = lower motor neuron; OT = occupational therapy; PT = physical therapy; SARA = Scale for the Assessment and Rating of Ataxia; UMN = upper motor neuron

1.

Table 8.

Recommended Surveillance for Individuals with SYNE1-Deficient Arthrogryposis Multiplex Congenita

System/Concern | Evaluation | Frequency

Neurologic

| Neurologic assessment | Annually; more often for an acute exacerbation

Physiatry, OT/PT assessment of mobility, self-help skills

Musculoskeletal

| Assess for:

Source: GeneReviews — "SYNE1 Deficiency"

Phenotype severity distribution: 15 always present features, 8 common features.