Diagnostic Criteria

Suggestive Findings

The diagnosis of Chediak-Higashi syndrome (CHS) should be suspected in a proband with any of the following clinical features, supportive laboratory findings, and family history.

Clinical features

Source: GeneReviews — "Chediak-Higashi Syndrome"

Differential Diagnosis

The diagnosis of Chediak-Higashi syndrome (CHS) should be considered in individuals with pigment dilution defects of the hair, skin, or eyes; congenital or transient neutropenia; immunodeficiency; and otherwise unexplained neurologic abnormalities or neurodegeneration. Each of these findings may be variably represented or absent in affected individuals; therefore, heightened suspicion is needed to pursue an accurate diagnosis.

Table 3.

Genes of Interest in the Differential Diagnosis of Chediak-Higashi Syndrome

Gene(s) | Disorder | MOI | Clinical Features | Comment

AP3B1

AP3D1

BLOC1S3

BLOC1S5

BLOC1S6

DTNBP1

HPS1

HPS3

HPS4

HPS5

HPS6 | Hermansky-Pudlak syndrome (HPS) | AR | • OCA a bleeding diathesis secondary to absent platelet-dense bodies

Source: GeneReviews — "Chediak-Higashi Syndrome"

Management Guidelines

No clinical practice guidelines for Chediak-Higashi syndrome (CHS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Chediak-Higashi syndrome (CHS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Chediak-Higashi Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Ophthalmologic

| By pediatric or adult ophthalmologist depending on age | • Assess for signs of pigment (see OCA/OA Overview) refractive errors.

• Consider OCT to provide baseline retinal fiber thickness.

Immunologic

| Screening for history of frequent or unusual infections | Referral to immunologist /or hematologist/oncologist for consideration of eval for HSCT

Bleeding disorder

| By hematologist | Platelet aggregation studies /or platelet EM for dense body analysis

Neurologic

| By pediatric or adult neurologist depending on age | • Neurologic exam

• Specialized testing if abnormalities identified on clinical exam

Cognitive impairment

| Child | Developmental/educational assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ need for IEP /or 504 plan

Adult

| Neuropsychologist | Measures of mood, memory, attention, processing speed, ...

Source: GeneReviews — "Chediak-Higashi Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations in are recommended.

Table 6.

Chediak-Higashi Syndrome: Recommended Surveillance

System/Concern | Evaluation | Frequency

Ocular

| Ophthalmologic exam | At least annually or as directed by treating ophthalmologist

Skin | Dermatologic exam for routine monitoring of persons w/hypopigmentation | At least annually

Hematology/Oncology

| Post HSCT: monitoring of chimerism1,2 ongoing post-transplant follow up | According to local center recommendations

If persons have not undergone HSCT, monitor for signs of HLH using combination of:

• Abdominal ultrasound

• Complete blood count

• Ferritin concentration

• Serum triglycerides

• Fibrinogen level

• Soluble interleukin-2 receptor level

Consider bone marrow biopsy if findings of above studies suggest HLH. | At least annually, but more frequently if changes in clinical status

Education

| Monitor developmental progress educational needs. | At each visit

Cognitive issues

| By primary care physician or psychologist/neuropsychologist | If changes in clinical status

Neurologic

| Neurologic exam for signs of peripheral neuropathy, ataxia, signs suggestive of parkinsonism, or other changes from baseline daily functioning independence | Specialized testing at discretion of treating neurologist based on clinical findings

Musculoskeletal

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

Family/Community

| Assess ...

Source: GeneReviews — "Chediak-Higashi Syndrome"