Diagnostic Criteria

Note: This chapter on PAFAH1B1-related lissencephaly/ subcortical band heterotopia (SBH) excludes Miller-Dieker syndrome. The term "Miller-Dieker syndrome" is frequently used to refer to individuals with larger deletions of 17p13.3 that include both PAFAH1B1 and YWHAE (a region of about 1.3 Mb harboring many genes) .

Suggestive Findings

PAFAH1B1-related lissencephaly/SBH should be suspected in individuals with the following clinical and MRI findings.

Clinical features (nonspecific)

Source: GeneReviews — "PAFAH1B1-Related Lissencephaly/ Subcortical Band Heterotopia"

Differential Diagnosis

The greatest difficulty in the diagnosis of lissencephaly and subcortical band heterotopia (SBH) is recognizing the malformation. Lissencephaly is subdivided into several types depending on gradient and grade of gyral malformation and cortical thickness . Several different cortical malformations that are sometimes mistaken for lissencephaly have been described, including severe congenital microcephaly with reduced number of gyri, cobblestone malformations as seen in Walker-Warburg and other syndromes, polymicrogyria, and polymicrogyria-like variants associated with pathogenic variants of tubulin genes. This leads to inefficient molecular testing and incorrect diagnosis and counseling. Clinical features can help distinguish children who have lissencephaly from those who have other brain malformations. Children with lissencephaly usually have normal or slightly small OFC at birth (-3 SD) and diffuse hypotonia except for mildly increased tone at the wrists and ankles. Children with severe congenital (i.e., primary) microcephaly and gyral abnormalities have smaller birth OFC (≤-3 SD) and may be hypotonic or spastic. Infants with polymicrogyria, especially when the frontal lobes are involved, frequently have spastic quadriparesis. Brain imaging (preferably by MRI) and/or neuropathologic examination during autopsy is necessary to confirm a diagnosis of lissencephaly. Classic Lissencephaly The differential diagnosis of classic lissencephaly is summarized in . These disorders are distinguished by mode of inheritance, grade and gradient of lissencephaly or SBH (see Clinical Description, ), presence of other congenital anomalies, clinical features, and results of molecular genetic testing. Table 3. Genes of Interest in the Differential Diagnosis of Classic Lissencephaly

Management Guidelines

No consensus management recommendations for PAFAH1B1-related lissencephaly/ subcortical band heterotopia (SBH) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with PAFAH1B1-related lissencephaly/SBH, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with PAFAH1B1-Related Lissencephaly/ Subcortical Band Heterotopia

Source: GeneReviews — "PAFAH1B1-Related Lissencephaly/ Subcortical Band Heterotopia"

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with PAFAH1B1-Related Lissencephaly/ Subcortical Band Heterotopia

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Gastrointestinal

| Monitor for constipation.

Respiratory

| Monitor for evidence of aspiration, respiratory insufficiency.

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations incl unusual spells or developmental regression.1

Development

| Monitor developmental progress educational needs.

Musculoskeletal

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

Miscellaneous/

Other

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

Eyes | Ophthalmologic eval | Annually or as clinically indicated

Hearing

| Audiologic eval

OT = occupational therapy; PT = physical therapy

1. If present, a neurology consultation should be performed and an EEG considered.

Source: GeneReviews — "PAFAH1B1-Related Lissencephaly/ Subcortical Band Heterotopia"