Chromosome 12q12 Deletion

12q12 Deletion

chromosome 12

Deletions of the q12 segment on the long arm of chromosome 12 cause a variety of clinical features, with the most common being neurodevelopmental concerns and other delays¹.

Individuals with 12q12 deletions frequently have some extent of neurodevelopmental delays. Neurological concerns include hypotonia (68%), psychomotor delays (68%), speech disorder (87.5%), and intellectual delays (83%)¹. Although a developmental timeline may be slower (such as head control at 7 months, sitting unsupported at 13 months, and walking with assistance at 18 months), it is still common for individuals with 12q12 deletions to achieve motor milestones². It should also be noted that if intellectual delays are present, they are often mild and, in their absence, patients may have other learning delays¹.

Less common neurological concerns include epilepsy (8%) or brain MRI abnormalities (ventriculomegaly, delayed myelination, or posterior pituitary agenesis)¹. Behavioral problems including autism, attention deficit hyperactivity disorder (ADHD), aggressive behavior, and anxiety disorders have also been described¹.

In addition to these neurodevelopmental concerns, facial dysmorphism may be seen in those with 12q12 deletions. This includes coarse facial features, a wide mouth, down-slanted palpebral fissures, broad nasal bridge, low set posteriorly rotated ears, and downturned corners of the mouth^1,3. Additionally, widely spaced nipples, fifth finger clinodactyly, small hands, and small feet have also been described³.

While less common, 12q12 deletions may also cause various ophthalmic, skeletal, and cardiology concerns. Ophthalmic features include ptosis (11%), myopia (24%), hyperopia (22.5%), strabismus (29%), and astigmatism (7.5%)¹. Ectodermal features include dental, gingival, and jaw anomalies (49%), hair anomalies (50%), and nail anomalies (51%)¹. Short stature (36.5%) and small abnormalities of the hands and feet revealed upon X-ray examination are the most common skeletal features¹. Lastly, almost 23% of patients have heart problems, including atrial septal defect, partial atrioventricular canal defect, and abnormal morphology of the coronary arteries¹.

It is thought that the ARID2 gene is responsible for the features associated with 12q12 deletions. ARID2 is located within the 12q12 region and participates in a variety of cellular processes including transcription regulation, cell proliferation, and cell line differentiation¹. It is highly expressed in cells of the heart, stomach, esophagus, fetal testis, and fetal brain⁴.

Deletions of 12q12 and point mutations in the ARID2 gene may be presented as “AIRD2-related disorder”^1,4.

REFERENCES

¹Houdayer C, Rooney K, van der Laan L, et al. (2025). ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature. Eur J Hum Genet., Advance online publication.

²Gallego M, Barreiro C, Pérez M, et al. (2000). A new case of interstitial 12q Deletion. Int Pediatr. 15(1): 37-40.

³Weng Y, Luo X, Hou L. (2018). Deletion at 12q12 increases the risk of developmental delay and intellectual disability. Ann Hum Genet. 82(6): 482–487.

⁴Gazdagh G, Blyth M, Scurr I, et al. (2019). Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients. Eur J Med Genet. 62(1): 27–34.