Clinical Guidance

No genotype-phenotype correlations distinguish individuals with pathogenic sequence variants from those with MBD5 deletions. Individuals with larger deletions involving multiple genes may exhibit a more severe phenotype.

Source: GeneReviews — "MBD5 Haploinsufficiency"

Penetrance

Penetrance is predicted to be complete.

Source: GeneReviews — "MBD5 Haploinsufficiency"

Diagnostic Criteria

Suggestive Findings

MBD5 haploinsufficiency, a neurodevelopmental disorder, should be suspected in individuals with the following findings .

Neurologic

• Motor delays

• Severe speech and language impairment

• Intellectual disability (ID), usually moderate to severe

• Seizures

• Sleep disturbance

• Hypotonia

• Feeding difficulties, often related to hypotonia

Behavior

• Short attention span

• Autistic-like behaviors that include gaze avoidance, inattention, and repetitive behaviors

• Self-injury and/or aggressive behaviors

Establishing the Diagnosis

The diagnosis of MBD5 haploinsufficiency is established in a proband with one of the following :

Source: GeneReviews — "MBD5 Haploinsufficiency"

Differential Diagnosis

Because the phenotypic features associated with MBD5 haploinsufficiency are not sufficient to diagnose this condition, all disorders with intellectual disability without other distinctive findings should be considered in the differential diagnosis. See OMIM Autosomal Dominant, Autosomal Recessive, and Nonsyndromic X-Linked Intellectual Developmental Disorder Phenotypic Series.

Source: GeneReviews — "MBD5 Haploinsufficiency"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MBD5 haploinsufficiency, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with MBD5 Haploinsufficiency

Source: GeneReviews — "MBD5 Haploinsufficiency"

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 — "MBD5 Haploinsufficiency"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with MBD5 Haploinsufficiency

System/Concern | Evaluation | Frequency

Development

| • Monitor developmental progress educational needs.

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

| At each visit /or as needed

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new seizures.

| At each visit

Neurobehavioral/

Psychiatric

| • Assessment for sleep disturbance

• Assessment for anxiety, attention, aggressive or self-injurious behavior

Feeding/

Gastrointestinal

| • Eval of nutritional status

• Monitor for constipation.

Musculoskeletal

| Clinical assessment for scoliosis | Annually throughout childhood

Family/

Community

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

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "MBD5 Haploinsufficiency"