Diagnostic Criteria

SYNE1 deficiency comprises a phenotypic spectrum that ranges from autosomal recessive cerebellar ataxia to arthrogryposis multiplex congenita (AMC).

Suggestive Findings

SYNE1 deficiency should be suspected in individuals with a combination of the following clinical features and/or clinical syndrome based on age of onset.

Clinical features

Source: GeneReviews — "SYNE1 Deficiency"

Differential Diagnosis

Table 2. Disorders to Consider in the Differential Diagnosis of SYNE1 Deficiency

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with SYNE1 deficiency, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with SYNE1-Deficient Cerebellar Ataxia

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"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SYNE1 Deficiency"

Surveillance Guidelines

There are no published surveillance guidelines for individuals with SYNE1 deficiency or for degenerative ataxias in general.

Table 7.

Recommended Surveillance for Individuals with SYNE1 Deficient Cerebellar Ataxia

System/Concern | Evaluation | Frequency

Neurologic

| • Neurologic assessment for progression of ataxia; UMN or LMN signs

• 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"