Clinical Guidance

MSX2. No prominent genotype-phenotype correlation exists between different MSX2 pathogenic loss-of-function variants causing enlarged parietal foramina. However, unique pathogenic variants in single families have been associated with aplasia cutis congenita and clavicular hypoplasia , possibly suggesting subtle dominant-negative effects. ALX4.

Source: GeneReviews — "Enlarged Parietal Foramina"

Penetrance

Penetrance for MSX2 and ALX4 heterozygous pathogenic variants is age related (as the relative width of the defects decreases with age) and high, but reduced (several individuals with a documented pathogenic variant showed no radiographic evidence of enlarged parietal foramina) .

Source: GeneReviews — "Enlarged Parietal Foramina"

Diagnostic Criteria

No consensus clinical diagnostic criteria for enlarged parietal foramina have been published. In practice, confounding with minute parietal foramina, which are normal anatomic variations, is very unlikely given the size, location, and natural history of the defects, as well as the positive family history.

Suggestive Findings

Enlarged parietal foramina should be suspected in probands with the following clinical and imaging findings and family history. Clinical findings. A palpable, soft, flattened region behind the apex of the skull, symmetric across the midline; the bony border may be palpable.

Imaging findings

Source: GeneReviews — "Enlarged Parietal Foramina"

Differential Diagnosis

Isolated enlarged parietal foramina need to be distinguished from syndromic associations, including those described in . Skeletal dysplasias with consistently broad skull defects and/or wide-open sutures and fontanelles that do not represent or evolve into enlarged parietal foramina, such as classic cleidocranial dysplasia (see Cleidocranial Dysplasia Spectrum Disorder), osteolytic conditions, and metabolic bone disorders, are unlikely to be in the ordinary differential diagnosis scope.

Table 3.

Syndromes with Enlarged Parietal Foramina to Consider in the Differential Diagnosis of Isolated Enlarged Parietal Foramina

Gene/Genetic Mechanism | Disorder | MOI | Clinical Features

Proximal 11p deletion | Potocki-Shaffer syndrome (OMIM 601224) | AD | See .

Source: GeneReviews — "Enlarged Parietal Foramina"

Management Guidelines

No clinical practice guidelines for enlarged parietal foramina have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder, together with review of the literature.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with enlarged parietal foramina, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Enlarged Parietal Foramina: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Skeletal

| • Skull radiographs

• Skull 3D CT w/bone windows

|

Neurologic

| • Assess for seizures.

• Brain imaging using CT or MRI as needed to assess for meningeal, cortical, vascular malformations of posterior fossa

|

Integument

| Assess for scalp defect. |

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of enlarged parietal foramina to facilitate medical personal decision making

MOI = mode of inheritance

1. Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Treatment of Manifestations

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in rel...

Source: GeneReviews — "Enlarged Parietal Foramina"

Clinical Guidance

Contact sports should be avoided if a midline bony defect persists.

Source: GeneReviews — "Enlarged Parietal Foramina"

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 — "Enlarged Parietal Foramina"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 6.

Enlarged Parietal Foramina: Recommended Surveillance

System/Concern | Evaluation | Frequency

Enlarged parietal foramina

| Assess defect clinically; follow-up radiographs rarely required. | Every 6-12 mos until natural history established

Neurologic

| Assess for seizures, headache, or other concerning clinical manifestations. | Only if symptomatic

Source: GeneReviews — "Enlarged Parietal Foramina"