Penetrance

Penetrance for IRF2BPL-related disorder appears to be high; however, substantial intrafamilial and interfamilial variability in age of onset and clinical features has been observed. Developmental delay and intellectual disability were reported in a female with an IRF2BPL pathogenic variant inherited from her apparently unaffected mother who died at age 45 years of an unrelated cause . Possible reduced penetrance has been observed in several additional families [LDM Pena P Marcogliese, personal observations].

Source: GeneReviews — "IRF2BPL-Related Disorder"

Diagnostic Criteria

Suggestive Findings

IRF2BPL-related disorder should be considered in probands with the following clinical and imaging findings and family history.

Clinical findings in individuals presenting at age 18 years

Source: GeneReviews — "IRF2BPL-Related Disorder"

Differential Diagnosis

Because IRF2BPL-related disorder is clinically indistinguishable from many other inherited disorders with similar neurologic findings, diagnosing this condition on clinical grounds only without molecular genetic testing is not feasible. All disorders with neurodevelopmental features and/or ataxia without other distinctive findings should be considered in the differential diagnosis. See:

• OMIM Phenotypic Series:

• Autosomal dominant intellectual developmental disorder

• Autosomal recessive intellectual developmental disorder

• Nonsyndromic X-linked intellectual developmental disorder

• Syndromic X-linked intellectual developmental disorder

• Developmental and epileptic encephalopathy

• Hereditary Ataxia Overview

Selected disorders with a high degree of clinical overlap are listed in .

Table 3.

Source: GeneReviews — "IRF2BPL-Related Disorder"

Management Guidelines

No clinical practice guidelines for IRF2BPL-related disorder 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 IRF2BPL-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

IRF2BPL-Related Disorder: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Development

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

• Eval for early intervention/ special education

• For persons age 5 yrs: consider baseline neurocognitive eval

Neurologic

| Neurologic eval | • To incl brain MRI

• Consider EEG if seizures are a concern. Note: Abnormal EEG may precede clinical seizures.

• Consider dedicated movement disorder eval.

Movement disorder/ Spasticity/ Contractures

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

• Gross motor fine motor skills

• Contractures

• Mobility, ADL, need for adaptive devices

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

Dysarthria

| Speech eval | Consider communication device or alternative mode of communication.

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for concerns incl findings suggestive of ASD, ADHD, ...

Source: GeneReviews — "IRF2BPL-Related Disorder"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. IRF2BPL-Related Disorder: Recommended Surveillance

Source: GeneReviews — "IRF2BPL-Related Disorder"