Enlarged parietal foramina (ORPHA:60015)
Enlarged parietal foramina (EPF) is a developmental defect, characterized by variable intramembranous ossification defects of the parietal bones, which is either asymptomatic, symptomatic (headaches, nausea, vomiting, intellectual disability) or associated with other pathologies.
Epidemiology
Prevalence is estimated to be 1/15,000-1/50,000.
Clinical description
EPF is a congenital disorder characterized by symmetrical, paired persistent foramina (openings) in the parietal bones (diameter >5 mm), located close to the intersection of the sagittal and lambdoid sutures. In infants, EPF presents as a persistent enlargement extending forward from the posterior fontanelle, caused by a single large central parietal bone defect, termed cranium bifidum. The latter tends to resolve in early childhood leaving two distinct, large parietal foramina through the ossification of a midline bridge. EPF is usually asymptomatic, but may be associated with headaches, nausea, vomiting, intense local pain and intellectual disability. EPF can also be accompanied by meningeal, cortical, and vascular malformations of the posterior fossa (that may predispose to epilepsy), and Duane retraction syndrome (see this term). Craniofacial anomalies including cleft palate, myelomeningocele and isolated encephalocele are rarely associated (see these terms). Clavicular hypoplasia may lead to confusion with cleidocranial dysplasia (see this term).
Etiology
EPF is caused by insufficient ossification around the parietal notch. In most cases this results from heterozygous loss of function mutations in human homeobox genes, MSX2 (5q35.2) and ALX4 (11p11.2), which encode transcription factors involved in skeletal development. A possible third locus on 4q21-q23 has also been reported in a large Chinese pedigree. EPF may also be seen in aminopterin/methotrexate embryofetopathy (see this term), which is caused by exposure to folic acid antagonists during the first trimester of preganancy.
Diagnostic methods
Diagnosis of EPF is based on family history and on clinical examination. Radiographically, EPF presents as symmetric radiolucencies. Computed tomography (CT) imaging with 3D reconstructions can delineate the osseous defect and magnetic resonance (MR) imaging may demonstrate associated intracranial changes. If EPF is associated with anomalies of the cerebral vasculature, additional vascular imaging like CT, MR, or digital subtraction angiography may be warranted. Diagnosis is confirmed by screening for the pathogenic mutation.
Differential diagnosis
Differential diagnosis includes Potocki-Shaffer syndrome; distal monosomy 15q; cleidocranial dysplasia; acromelic frontonasal dysplasia; craniosynostosis-anal anomalies-porokeratosis; and frontonasal dysplasia with alopecia and genital anomaly (see these terms).
Antenatal diagnosis
Preimplantation genetic testing, or prenatal diagnosis during pregnancy from 10 weeks gestation, is available for families with a known genetic defect.
Genetic counseling
Transmission is autosomal dominant with high but incomplete penetrance.
Management and treatment
Treatment for EPF is generally conservative, since the natural history of the defect is to close progressively with age. Protective helmets can be considered in young, active children with particularly large defects, but surgery is not usually recommended. Imaging to assess for any accompanying venous anomalies is imperative prior to any surgical intervention.
Prognosis
There is no known correlation between the size of the defect and the likelihood of having an associated brain abnormality. A spontaneous closure of the defect with growth of the infant has been observed, but it is frequently incomplete.

                            Last update: 
                            October 2014


                            - Expert reviewer(s): 
                            Dr Tracy LESTER  - Pr Andrew WILKIE