The gene on chromosome 11p11.2 that encodes ALX homeobox 4 (OMIM:605420, UniProtKB:Q9H161), a homeodomain transcription factor involved in skull and limb development, which plays a key role in craniofacial, skin and hair follicle development and mesenchymal-epithelial communication.
Molecular pathology Defects of ALX4 cause:
• Craniosynostosis 5 An autosomal dominant abnormality (OMIM:615529) of skull growth characterised by premature fusion of one or more cranial sutures. Growth of the developing brain may outpace that of the skull, resulting in goofy looking heads and often increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental defects.
large parietal foramina superior and slightly medial to the orbits
• Frontonasal dysplasia 2 An autosomal recessive condition (OMIM:613451) characterised by midfacial dysraphia, with ocular hypertelorism, broad nasal root, median facial cleft affecting the nose and/or upper lip and palate; uni- or bilateral clefting of the alae nasi, absence of nasal tip, anterior cranium bifidum occultum, and a V-shaped or widow’s peak frontal hairline.
• Parietal foramina 2 An autosomal dominant (OMIM:609597) disease characterised by deficient ossification of the parietal bone (image, right), frontonasal dysplasia with alopecia and hypogonadism.
• Potocki-Shaffer syndrome A contiguous gene deletion syndrome (OMIM:601224) caused by a haploinsufficiency of the 11p12-p11.2 chromosome region which includes the ALX4 gene.