Ruijs–Aalfs syndrome
| Ruijs–Aalfs syndrome | |
|---|---|
 | |
| Autosomal recessive pattern is the inheritance manner of this condition. | |
| Specialty | Medical genetics |
| Causes | Mutations in the SPRTN gene |
Ruijs–Aalfs syndrome (RJALS) is a rare condition characterised by facial and skeletal abnormalities along with the development of hepatoma in the teenage years.
Signs and symptoms
The main features of this condition are evident in skeleton and face[1]
Facial features:
- Triangular face
- Small frontotemporal diameter
- Small deep set eyes
- Bulbous nose with high nasal bridge
- Small upper lip
- Micrognathia
Skeletal features:
- Thoracic kyphoscoliosis
- Sloping shoulders
- Pectus excavatum
- Elbow contractures
- Clinodactyly
- Pes planus
- Delayed bone age
Other associated conditions:
- Lipodystrophy
- Simian creases
All three patients developed liver cancer (hepatoma) in the teens.
Genetics
This condition has been associated with mutations in the Spartan gene (SPRTN). This gene is located on the long arm of chromosome 1 (1q42.2). The gene SPRTN encodes the DNA dependent metalloprotease Spartan. Spartan is intimately involved in the repair of protein-linked DNA breaks.[2]
Pathophysiology
The syndrome is caused by mutations in the SPRTN gene, causing the loss of function in the Spartan protein. Since the Spartan protein is involved in the repair of DNA-protein crosslinks, the loss of function allows proteins to remain bonded to DNA, causing increased risk to cancer, as well as other genetic defects. [3]
Diagnosis
This syndrome may be suspected on clinical grounds. The diagnosis is established by sequencing the SPRTN gene[4]
Differential diagnosis
Treatment
There is no specific treatment for this condition. Management is supportive.[5]
Epidemiology
This condition is considered to be rare, with only 3 cases reported in the literature.[6]
History
This condition was first described in 2003.[7]
References
- ↑ Lessel D, Vaz, B, Halder S, Lockhart PJ, Marinovic-Terzic I, Lopez-Mosqueda J, Philipp M, Sim JCH, Smith KR, Oehler J, Cabrera, E, Freire R, et al. (2014) Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. Nature Genet. 46: 1239-1244
- ↑ Abugable AA, Morris JLM, Palminha NM, Zaksauskaite R, Ray S, El-Khamisy SF. DNA repair and neurological disease: From molecular understanding to the development of diagnostics and model organisms. DNA Repair (Amst). 2019 Sep;81:102669. doi:10.1016/j.dnarep.2019.102669. Epub 2019 Jul 8. Review. PMID 31331820
- ↑ Maskey, Reeja S.; Flatten, Karen S.; Sieben, Cynthia J.; Peterson, Kevin L.; Baker, Darren J.; Nam, Hyun-Ja; Kim, Myoung Shin; Smyrk, Thomas C.; Kojima, Yusuke; Machida, Yuka; Santiago, Annyoceli; van Deursen, Jan M.; Kaufmann, Scott H.; Machida, Yuichi J. (2017-05-05). "Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis". Nucleic Acids Research. 45 (8): 4564–4576. doi:10.1093/nar/gkx107. ISSN 0305-1048. PMC 5416836. PMID 28199696.
- ↑ "Ruijs-Aalfs Syndrome". www.orpha.net. Retrieved 2026-07-11.
- ↑ "Ruijs Aalfs Syndrome (Progeroid Features - Hepatocellular Carcinoma Predisposition Syndrome): Symptoms, Diagnosis and Treatment". Symptoma. Retrieved 2026-07-11.
- ↑ "Ruijs-Aalfs Syndrome – FindZebra". www.findzebra.com. Retrieved 2026-07-11.
- ↑ Ruijs MWG, van Andel RNJ, Oshima J, Madan K, Nieuwint AWM, Aalfs CM (2003) Atypical progeroid syndrome: an unknown helicase gene defect? Am J Med Genet 116A: 295-299