Diagnostic Criteria

Suggestive Findings

Diagnosis of EXOSC3 pontocerebellar hypoplasia (EXOSC3-PCH) should be suspected in children with and characteristic .

Neurologic Findings

Common

• Hypotonia (onset is usually at birth, but a later onset is possible)

• Signs of neurogenic muscle atrophy, such as muscle atrophy and decreased tendon reflexes

• Central motor neuron signs (spasticity, dystonia), especially in individuals with prolonged survival

• Lower motor neuron involvement, demonstrated by EMG (abnormal EMG potentials, increased motor unit potentials, fasciculations)

Less common

• Joint contractures (can be present at birth or develop later)

• Swallowing insufficiency

• Ophthalmologic findings of:

• Small or pale optic discs indicative of optic atrophy

• Nystagmus

• Strabismus

• Seizures

Source: GeneReviews — "EXOSC3 Pontocerebellar Hypoplasia"

Differential Diagnosis

Key disorders to consider in the differential diagnosis of pontocerebellar hypoplasia type 1 (PCH1) include EXOSC8-, SLC25A46-, and VRK1-related PCH1, PCH2/4 (TSEN54-related PCH), spinal muscular atrophy type 1, PCH10, and PCH12 . PCH1. About 50% of individuals with PCH1 have pathogenic variants in EXOSC3 (i.e., EXOSC3-PCH). In children with EXOSC3-PCH, neonatal death, delayed nerve conduction velocities, and congenital respiratory and feeding difficulties occur less frequently than in those without identifiable EXOSC3 pathogenic variants . PCH2/4. Dyskinesias and seizures are common in PCH2, the most common type of PCH. PCH4 is a severe form of PCH2, often with congenital contractures and polyhydramnios. In children with EXOSC3-PCH, central motor findings (together with the typical brain MRI findings of cerebellar or pontocerebellar hypoplasia) may falsely suggest a diagnosis of PCH2. Compared to findings in EXOSC3-PCH, the findings in PCH2 are: • No abnormalities of the spinal cord (whereas in PCH1 anterior horn cells are involved); • Attenuation of the pons on brain MRI (whereas in PCH1 the pons can be unaffected). Table 2. Genes of Interest in the Differential Diagnosis of EXOSC3 Pontocerebellar Hypoplasia

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with EXOSC3 pontocerebellar hypoplasia (EXOSC3-PCH), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of EXOSC3 Pontocerebellar Hypoplasia

Source: GeneReviews — "EXOSC3 Pontocerebellar Hypoplasia"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with EXOSC3 Pontocerebellar Hypoplasia

System/Concern | Evaluation | Frequency

Respiratory

| Assess airway pulmonary function secretion management. | Monitoring of respiratory function may be necessary to detect sleep apnea.

Gastrointestinal/

Feeding

|

• Aspiration risk nutritional status

• Monitor for constipation.

| Annually; more frequently if needed

Musculoskeletal

|

• PT/OT eval

• Assess for contractures, scoliosis, foot deformities.

• Hip/spine x-rays

Neurologic

|

• Monitor those w/seizures as clinically indicated.

• Monitor for dystonia choreic movements.

Development

| Monitor developmental milestones

Family support

resources | Family needs

OT = occupational therapy, PT = physical therapy

Source: GeneReviews — "EXOSC3 Pontocerebellar Hypoplasia"