Clinical Guidance

No clear genotype-phenotype correlation has been identified to date. However, the following have been noted:

• Individuals with a large, cytogenetically visible Xq28 duplication have growth deficiency, microcephaly, and urogenital anomalies in addition to those findings described in .

• A more important correlation with clinical severity is MECP2 copy number, as triplication of the MECP2 region apparently results in a more severe phenotype .

Source: GeneReviews — "MECP2 Duplication Syndrome"

Penetrance

MECP2 duplications are believed to be completely penetrant in males.

Source: GeneReviews — "MECP2 Duplication Syndrome"

Diagnostic Criteria

Suggestive Findings

MECP2 duplication syndrome should be considered in males with the following clinical findings:

• Severe-to-profound intellectual disability with limited or absent speech

• Early-onset hypotonia with very slow motor development

• Progressive spasticity predominantly of the lower limbs

• Predisposition to infections manifest as recurrent respiratory infections (in 75% of affected males)

• Epileptic seizures (in 50%)

• Other variably present features including autistic features, gastrointestinal dysfunction, and mild facial dysmorphism

Source: GeneReviews — "MECP2 Duplication Syndrome"

Differential Diagnosis

Because the phenotypic features associated with MECP2 duplication syndrome 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, Nonsyndromic X-Linked, and Syndromic X-Linked Intellectual Developmental Disorder Phenotypic Series. Int22h1/int22h2-mediated Xq28 duplication syndrome. Several other recurrent duplications involving the X chromosome and resulting in X-linked intellectual disability in males have been identified. On chromosome fragment Xq28, the int22h1/int22h2-mediated Xq28 duplication syndrome has been described, caused by 0.

Source: GeneReviews — "MECP2 Duplication Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MECP2 duplication syndrome, 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 MECP2 Duplication Syndrome

Source: GeneReviews — "MECP2 Duplication Syndrome"

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 — "MECP2 Duplication Syndrome"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with MECP2 Duplication Syndrome

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Gastrointestinal

| Monitor for constipation reflux.

Development

| Monitor developmental progress educational needs.

Musculoskeletal

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

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures, changes in tone, spasticity.

Immunologic

| Assess frequency type of infections.

Psychiatric/

Behavioral

| Behavioral assessment for anxiety, attention, autistic-like features

Miscellaneous/

Other

| 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 — "MECP2 Duplication Syndrome"