Clinical Guidance

The effect of pathogenic variant(s) on the protein STAMBP likely influences the severity of the MIC-CAP syndrome phenotype, with complete absence of protein production leading to the most severe phenotypes. One affected female had a milder phenotype with moderate developmental delay and a less severe form of epilepsy . At birth her head circumference was within the normal range (1.8 SD); at her last evaluation at age five years, head circumference was 2.5 SD. She is able to walk independently and can speak in short phrases. She has approximately 30 capillary malformations of the skin and characteristic hypoplastic fingers and toes. She has a homozygous noncoding intronic pathogenic variant (c.

Source: GeneReviews — "Microcephaly-Capillary Malformation Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for microcephaly-capillary malformation (MIC-CAP) syndrome have been published.

Suggestive Findings

MIC-CAP syndrome should be suspected in individuals with the following clinical and neuroimaging findings and family history.

Clinical findings

Source: GeneReviews — "Microcephaly-Capillary Malformation Syndrome"

Differential Diagnosis

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome, an autosomal dominant disorder caused by a heterozygous pathogenic variant in EPHB4 or RASA1, is characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations mostly on the face and limbs. About 24% of affected individuals also have associated arteriovenous malformations and/or arteriovenous fistulas, fast-flow vascular anomalies that typically arise in the skin, muscle, bone, spine, and brain. Life-threatening complications of these lesions can include bleeding, congestive heart failure, and/or neurologic consequences. Unlike individuals with MIC-CAP syndrome, individuals with CM-AVM syndrome are not microcephalic and do not have intractable epilepsy or neurologic impairment.

Source: GeneReviews — "Microcephaly-Capillary Malformation Syndrome"

Management Guidelines

No clinical practice guidelines for microcephaly-capillary malformation (MIC-CAP) syndrome have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with microcephaly-capillary malformation (MIC-CAP) syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with Microcephaly-Capillary Malformation Syndrome

Source: GeneReviews — "Microcephaly-Capillary Malformation Syndrome"

Clinical Guidance

Valproic acid. One individual with MIC-CAP syndrome died from complications of pancreatitis after starting valproic acid for seizures . However, several other individuals with MIC-CAP syndrome have been treated with valproic acid without adverse effects. Therefore, it is unclear whether or not an association exists between MIC-CAP syndrome and adverse outcomes with valproic acid therapy. The benefits of use of valproic acid for seizure management in some patients may outweigh the potential risk for serious complications.

Source: GeneReviews — "Microcephaly-Capillary Malformation 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 — "Microcephaly-Capillary Malformation Syndrome"

Surveillance Guidelines

Table 4.

Recommended Surveillance for Individuals with Microcephaly-Capillary Malformation Syndrome

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations (e.g., seizures, changes in tone, movement disorders).

Development

| Monitor developmental progress educational needs.

Musculoskeletal

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

Family/

Community

| 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 — "Microcephaly-Capillary Malformation Syndrome"