3p25 deletion syndrome is likely to be very rare. Around 50 people have been identified with 3p25 deletion. However, this syndrome is likely under-diagnosed because some people with the deletion are not or only mildly affected.

The cause of 3p25 deletion syndrome is the deletion of the genetic material on the terminal region of the short arm (or p arm) of chromosome 3. In the majority of the cases, the deletion is not inherited from either parent and presents for the first time in the affected individual (also known as de novo). The deletion only needs to be present on one of the chromosome 3 for the disease to manifest. 

Researchers have been working to identify genes in the deletion region that are responsible for the disease. 4-71 genes can be deleted in patients with 3p25 deletion syndrome. Many of the deleted genes play essential roles in brain development and cognition. In particular, SETD5 is located in this region, and the loss or mutations of SETD5 are associated with autism, intellectual disability, and global developmental delay. Another gene that is sometimes deleted is VHL, which causes von Hippel-Lindau syndrome. People who have lost one copy of the VHL gene have increased susceptibility to tumors and abnormal blood vessel growth. Depending on which genes and the number of deleted genes, patients may experience different disease severity.

More than 80% of patients with 3p25 deletion syndrome have developmental delay, cognitive impairment, wide-set eyes, and drooping eyelids. More than 30% of the patients have a downturned mouth corner, cleft palate, weak muscle tone, and small brain. Other clinical presentations include seizures, autism spectrum disorder, hearing impairment, language impairment, intestinal problems, and congenital heart defects.

The diagnosis of 3p25 deletion syndrome is established by identifying the single allele deletion at the 3p25 position through analyses of patients’ chromosomes. 3p25 deletion syndrome can be diagnosed by karyotyping, which produces a chromosome image of the patient to identify large chromosomal deletions. Targeted deletion analyses such as fluorescence in situ hybridization (FISH) can also be used to detect smaller chromosomal deletion in combination with karyotyping.

Since 3p25 deletion syndrome can affect a broad range of organ systems of the body, a team of doctors is needed to manage the disease. Also, treatments and proper management are offered based on each patient’s unique clinical features. Notably, infants with delayed motor skills can be helped by occupational therapists. Kids with language impairment can be referred to a speech therapists. Behavioral therapy is often useful for affected patients with autism spectrum disorders.

Depending on the clinical manifestation of the disease, the long-term outlook for each person can vary significantly. A small number of people with 3p25 deletion develop normally and have no learning difficulties. For the majority of the cases, the disease severity depends on the size of the deletion and the genes involved. Early diagnosis and proper management of the symptoms can provide a better prognosis for the affected individuals.

3p25 Deletions. Unique. 2014; http://www.rarechromo.org/information/Chromosome%20%203/3p25%20deletions%20FTNW.pdf.

3p deletion syndrome. Genetics Home Reference

https://ghr.nlm.nih.gov/condition/3p-deletion-syndrome#diagnosis

Yagasaki H, Toda T, Koizumi K, et al. A de novo 10.1-Mb 3p25 terminal deletion including SETD5 in a patient with ptosis and psychomotor retardation. Pediatr Neonatol. 2018;59(3):319-321. doi:10.1016/j.pedneo.2017.09.004

Chou A, Toon C, Pickett J, Gill AJ. von Hippel-Lindau syndrome. Front Horm Res. 2013;41:30-49. doi:10.1159/000345668

Fernandes IR, Cruz ACP, Ferrasa A, Phan D, Herai RH, Muotri AR. Genetic variations on SETD5 underlying autistic conditions. Dev Neurobiol. 2018;78(5):500-518. doi:10.1002/dneu.22584