Clinical Guidance

No genotype-phenotype correlations have been identified.

Source: GeneReviews — "ASPM Primary Microcephaly"

Diagnostic Criteria

Suggestive Findings

ASPM primary microcephaly (ASPM-MCPH) should be suspected in individuals with the following clinical and neuroimaging findings.

Clinical findings

• Congenital microcephaly (usually identified before birth by ultrasound examination) with an occipitofrontal circumference ≥2 standard deviations (SD) below the mean at birth, and 3.5 SD below the mean before age one year

• Mild intrauterine growth restriction with postnatal catch up (Growth restriction does not persist after age two years.)

• No other congenital abnormalities

• Normal or subnormal motor development

• Usually mild intellectual disability (ID) with preserved memory but variable (range: borderline normal intellectual functioning to severe ID)

• Seizures (rare)

• Nonspecific facial features (i.e., narrow sloping forehead)

Source: GeneReviews — "ASPM Primary Microcephaly"

Differential Diagnosis

Monogenic disorders in the differential diagnosis of ASPM-MCPH include the primary microcephalies (PMs), a group of rare, phenotypically and etiologically heterogeneous disorders of brain growth characterized by (1) a head circumference close to or greater than 2 SD below the mean at birth and greater than 3 SD below the mean by age one year; (2) absence of extracephalic anomalies; and (3) mild-to-severe intellectual disability. Additional clinical or neuroimaging features can be associated. Most PMs are inherited in an autosomal recessive manner. To date, pathogenic variants in more than 100 genes are responsible for PM (for review, see ). The three broad phenotypic categories of monogenic primary microcephaly include the following:

Source: GeneReviews — "ASPM Primary Microcephaly"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ASPM primary microcephaly (ASPM-MCPH), 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 ASPM Primary Microcephaly

Source: GeneReviews — "ASPM Primary Microcephaly"

Clinical Guidance

Use of methylphenidate should be limited, as it exacerbates hyperactivity [Author, personal data].

Source: GeneReviews — "ASPM Primary Microcephaly"

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 — "ASPM Primary Microcephaly"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with ASPM Primary Microcephaly

System/Concern | Evaluation1

Feeding

| • Measurement of growth parameters (weight, height, OFC)

• Eval of nutritional status

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations incl new-onset seizures, spasticity, contractures (rare).

Development

| Monitor developmental progress educational needs.

Speech delay

| Monitor speech development.

Psychiatric/

Behavioral

| Ancillary behavior assessment for anxiety, attention, aggressive or self-injurious behavior; referral for formal eval if concerns

Musculoskeletal

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

Miscellaneous/

Other

| Assess family need for social work support (e.g., respite care, other local resources).

OFC = occipitofrontal circumference; OT = occupational therapy; PT = physical therapy

1. To be performed at each visit

Source: GeneReviews — "ASPM Primary Microcephaly"