5q31.3 microdeletion syndrome
5q31.3 microdeletion syndrome causes severe speech and motor delays, profound hypotonia, feeding and breathing difficulties, and frequent seizures due to loss of the PURA gene.
Overview
5q31.3 microdeletion syndrome is a very rare genetic condition characterized by markedly delayed development of speech and motor skills such as walking. Affected individuals present in infancy with weak muscle tone (hypotonia), feeding difficulties, and breathing problems that can be life‑threatening. The disorder also includes distinctive facial features and a high incidence of seizures and brain abnormalities related to myelin production.
Symptoms
- Severe delay in speech and walking
- Hypotonia (weak muscle tone) from infancy
- Feeding difficulties and dysphagia (trouble swallowing)
- Breathing problems that may be life‑threatening
- Distinctive facial features:
- Widely spaced eyes
- Open mouth with a tented (outward‑pointing) upper lip
- High‑arched palate
- Small lower jaw (micrognathia)
- Lack of facial expression (often linked to hypotonia)
- Recurrent seizures (epilepsy) and seizure‑like episodes (muscle jerking, twitching, stiffening)
- Brain abnormalities, often due to reduced production or delayed maturation of myelin
Causes & Risk Factors
5q31.3 microdeletion syndrome results from a chromosomal deletion on the long (q) arm of chromosome 5 at band q31.3. The deleted segment can range from several thousand to several million base pairs and typically removes at least three genes. The loss of one copy of the PURA gene is believed to produce most of the characteristic features.
The PURA gene encodes the protein Pur‑alpha (Purα), which has multiple cellular roles, including regulation of gene activity and assistance in DNA replication. Pur‑α is especially important for normal brain development, guiding the growth and division of nerve cells and possibly influencing myelin formation or maturation.
Haploinsufficiency of PURA likely disrupts normal neuronal development, leading to developmental delay, hypotonia, seizures, and other neurological problems. Some studies suggest that loss of additional nearby genes may increase severity, but the contribution of those genes remains unclear.
Inheritance
5q31.3 microdeletion syndrome follows an autosomal dominant pattern, meaning a single copy of the altered chromosome is sufficient to cause the disorder. The condition is typically not inherited; the deletion arises de novo during the formation of reproductive cells (eggs or sperm) or early fetal development, and most families have no prior history of the syndrome.
Other Names
- Severe neonatal hypotonia‑seizures‑encephalopathy syndrome due to 5q31.3 microdeletion
Additional Information & Resources
Genetic Testing Information
- Genetic Testing Registry: PURA‑related severe neonatal hypotonia‑seizures‑encephalopathy syndrome
Patient Support and Advocacy Resources
- National Organization for Rare Disorders (NORD)
Scientific Articles on PubMed
- PubMed
References
- Bonaglia MC, Zanotta N, Giorda R, D'Angelo G, Zucca C. Long‑term follow‑up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA. Mol Cytogenet. 2015 Nov 14;8:89. doi:10.1186/s13039-015-0193-9.
- Brown N, Burgess T, Forbes R, McGillivray G, Kornberg A, Mandelstam S, Stark Z. 5q31.3 Microdeletion syndrome: clinical and molecular characterization of two further cases. Am J Med Genet A. 2013 Oct;161A(10):2604‑2608. doi:10.1002/ajmg.a.36108.
- Hosoki K, Ohta T, Natsume J, Imai S, Okumura A, Matsui T, Harada N, Bacino CA, Scaglia F, Jones JY, Niikawa N, Saitoh S. Clinical phenotype and candidate genes for the 5q31.3 microdeletion syndrome. Am J Med Genet A. 2012 Aug;158A(8):1891‑1896. doi:10.1002/ajmg.a.35439.
- Shimojima K, Isidor B, Le Caignec C, Kondo A, Sakata S, Ohno K, Yamamoto T. A new microdeletion syndrome of 5q31.3 characterized by severe developmental delays, distinctive facial features, and delayed myelination. Am J Med Genet A. 2011 Apr;155A(4):732‑736. doi:10.1002/ajmg.a.33891.
- White MK, Johnson EM, Khalili K. Multiple roles for Puralpha in cellular and viral regulation. Cell Cycle. 2009 Feb 1;8(3):1‑7. doi:10.4161/cc.8.3.7585.