Clinical Guidance

Pathogenic variants leading to the complete absence of HYCC1 (formerly FAM126A) protein expression are associated with the full phenotype of bilateral cataract, central nervous system hypomyelination, and peripheral nerve hypomyelination. Pathogenic variants leading to a partial protein deficiency are associated with the milder form without peripheral nervous system involvement. An individual with deletion of exons 8 and 9 did not have congenital cataracts; cataracts developed at age nine years. A second individual had congenital unilateral cataract. However, of the four children in this family who survived beyond age two years, none was able to walk even with support after age six years .

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Penetrance

Penetrance is complete.

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Diagnostic Criteria

Suggestive Findings

Hypomyelination and congenital cataract (HCC) should be suspected in individuals with the following clinical findings and characteristic abnormalities on brain MRI .

Clinical findings

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Differential Diagnosis

The association of congenital cataract and CNS hypomyelination is typical of hypomyelination and congenital cataract (HCC). However, the differential diagnosis with other hypomyelinating disorders should include the disorders summarized in . MRI usually shows areas with an even higher T2-weighted signal in HCC, whereas the white matter signal is homogeneously hyperintense in other hypomyelinating disorders. Table 3. Hypomyelinating Disorders of Interest in the Differential Diagnosis of Hypomyelination and Congenital Cataract

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hypomyelination and congenital cataract (HCC), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with Hypomyelination and Congenital Cataract

System/Concern | Evaluation | Comment

Cataracts

| Ophthalmologic exam |

Developmental delay

| Developmental assessment | • Incl motor, adaptive, cognitive, speech-language eval for dysarthria

• Eval for early intervention/ special education

Neurologic

| Neurologic eval for evidence of spasticity, ataxia, seizures | Consider EEG if seizures are a concern.

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To incl assessment of:

• Gross motor fine motor skills

• Contractures, clubfoot, kyphoscoliosis

• Mobility, activities of daily living, need for adaptive devices

• Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

Gastrointestinal/

Feeding

| Gastroenterology/ nutrition/feeding team eval | • To incl eval of aspiration risk nutritional status

• Consider eval for gastrostomy tube placement in those w/dysphagia /or aspiration risk.

Genetic counseling

| By genetics professionals1 | To inform affected persons their families re nature, MOI, implications of HCC to facilitate medical personal decision making

Family support

resources | Assess need for:

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Clinical Guidance

None are known. Some individuals are prone to febrile seizures.

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Therapies Under Investigation

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

Source: GeneReviews — "Hypomyelination and Congenital Cataract"

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with Hypomyelination and Congenital Cataract

System/Concern | Evaluation | Frequency

Cataracts

| Eye exam if cataracts were not identified in the neonatal period |

Development

| Monitor developmental progress educational needs. | At each visit

Neurologic

| Monitor those w/seizures as clinically indicated.

Assess for new manifestations incl seizures, changes in tone, movement disorders.

Musculoskeletal

| Physical medicine, OT/PT assessment of mobility, self-help skills

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

Family/

Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) care coordination.

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "Hypomyelination and Congenital Cataract"