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Description
Wiedemann-Rautenstrauch syndrome is a type of progeria. People with progeria have certain features that make them look older than they are. The signs and symptoms of Wiedemann-Rautenstrauch syndrome begin before birth as affected individuals do not grow and gain weight at the expected rate (intrauterine growth restriction).
People with Wiedemann-Rautenstrauch syndrome have distinctive facial features that give the appearance of old age. They often have a triangular face
with a prominent forehead
and pointed chin, a small mouth with a thin upper lip
, a small jaw, low-set ears, and abnormal lower eyelids. In most affected individuals, the middle of the face looks as though it is drawn inward (midface retraction). On the head, hair is sparse,
and the veins are prominent.
In people with Wiedemann-Rautenstrauch syndrome, the spaces (fontanelles) between the skull bones (that are noticeable as "soft spots" on the heads of infants) are larger than normal. The fontanelles normally close in early childhood, but they may remain open in people with this condition. Individuals with Wiedemann-Rautenstrauch syndrome may appear to have an abnormally large head, but their head size is typically normal for their age (pseudohydrocephalus).
Some individuals with Wiedemann-Rautenstrauch syndrome have intellectual disabilities. Affected children may also have developmental disabilities.
Many affected infants are born with teeth (natal teeth); these teeth fall out a few weeks after birth. Some or all of their permanent (adult) teeth may never develop (hypodontia).
A lack of fatty tissue under the skin (lipodystrophy), particularly in the face, arms, and legs, can make people with Wiedemann-Rautenstrauch syndrome look older than they are. In addition, the skin is thin and translucent.
Some individuals with Wiedemann-Rautenstrauch syndrome develop joint abnormalities called contractures that can limit movement. Additionally, movement problems such as difficulty with coordination and balance (ataxia) or involuntary rhythmic shaking (tremor), can appear during childhood and worsen over time. Some people with Wiedemann-Rautenstrauch syndrome have vision or hearing problems.
While many people with Wiedemann-Rautenstrauch syndrome do not survive past infancy or early childhood, others live into their teens or twenties.
Frequency
Wiedemann-Rautenstrauch syndrome is a rare disorder, though its exact prevalence is unknown. Fewer than 100 affected individuals have been described in the scientific literature.
Causes
Wiedemann-Rautenstrauch syndrome is caused by variants (also called mutations) in the POLR3A gene. This gene provides instructions for making the largest piece (subunit) of an enzyme called RNA polymerase III. This enzyme is involved in the production of RNA, a chemical cousin of DNA. RNA polymerase III helps produce several forms of RNA, including those that assemble protein building
blocks (amino acids
) into proteins. This process is essential for the normal functioning and survival of cells in tissues throughout the body.
The POLR3A gene variants that cause Wiedemann-Rautenstrauch syndrome lead to the production of abnormal subunits. These abnormal subunits may not be able to form the RNA polymerase III enzyme, or they may create an enzyme that is unable to produce RNA. Reduced function of the RNA polymerase III molecule likely affects the development of many parts of the body. However, it is unclear how the POLR3A gene variants cause the specific signs and symptoms of Wiedemann-Rautenstrauch syndrome.
Inheritance
This condition is inherited in an autosomal recessive pattern
, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Congenital pseudohydrocephalic progeroid syndrome
- Neonatal progeroid syndrome
- Neonatal pseudo-hydrocephalic progeroid syndrome
- Neonatal pseudohydrocephalic progeroid syndrome
- WRS
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Jay AM, Conway RL, Thiffault I, Saunders C, Farrow E, Adams J, Toriello HV. Neonatal progeriod syndrome associated with biallelic truncating variants in POLR3A. Am J Med Genet A. 2016 Dec;170(12):3343-3346. doi: 10.1002/ajmg.a.37960. Epub 2016 Sep 9. Citation on PubMed
- Khan A, Al Shamsi B, Al Shehhi M, Kashgari AA, Al Balushi A, Al Dihan FA, Alghamdi MA, Manal A, Gonzalez-Alvarez AC, Arold ST, Eyaid W. Further delineation of Wiedemann-Rautenstrauch syndrome linked with POLR3A. Mol Genet Genomic Med. 2024 Mar;12(3):e2274. doi: 10.1002/mgg3.2274. Epub 2024 Feb 13. Citation on PubMed
- Lessel D, Ozel AB, Campbell SE, Saadi A, Arlt MF, McSweeney KM, Plaiasu V, Szakszon K, Szollos A, Rusu C, Rojas AJ, Lopez-Valdez J, Thiele H, Nurnberg P, Nickerson DA, Bamshad MJ, Li JZ, Kubisch C, Glover TW, Gordon LB. Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations. Hum Genet. 2018 Dec;137(11-12):921-939. doi: 10.1007/s00439-018-1957-1. Epub 2018 Nov 19. Citation on PubMed
- Paolacci S, Bertola D, Franco J, Mohammed S, Tartaglia M, Wollnik B, Hennekam RC. Wiedemann-Rautenstrauch syndrome: A phenotype analysis. Am J Med Genet A. 2017 Jul;173(7):1763-1772. doi: 10.1002/ajmg.a.38246. Epub 2017 Apr 26. Citation on PubMed
- Paolacci S, Li Y, Agolini E, Bellacchio E, Arboleda-Bustos CE, Carrero D, Bertola D, Al-Gazali L, Alders M, Altmuller J, Arboleda G, Beleggia F, Bruselles A, Ciolfi A, Gillessen-Kaesbach G, Krieg T, Mohammed S, Muller C, Novelli A, Ortega J, Sandoval A, Velasco G, Yigit G, Arboleda H, Lopez-Otin C, Wollnik B, Tartaglia M, Hennekam RC. Specific combinations of biallelic POLR3A variants cause Wiedemann-Rautenstrauch syndrome. J Med Genet. 2018 Dec;55(12):837-846. doi: 10.1136/jmedgenet-2018-105528. Epub 2018 Oct 15. Citation on PubMed
- Wambach JA, Wegner DJ, Patni N, Kircher M, Willing MC, Baldridge D, Xing C, Agarwal AK, Vergano SAS, Patel C, Grange DK, Kenney A, Najaf T, Nickerson DA, Bamshad MJ, Cole FS, Garg A. Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome. Am J Hum Genet. 2018 Dec 6;103(6):968-975. doi: 10.1016/j.ajhg.2018.10.010. Epub 2018 Nov 7. Citation on PubMed or Free article on PubMed Central
- Zea Vera A, Bruce A, Larsh TR, Jordan Z, Bruggemann N, Westenberger A, Espay AJ, Gilbert DL, Wu SW. Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders. Mov Disord Clin Pract. 2022 Dec 23;10(2):316-322. doi: 10.1002/mdc3.13635. eCollection 2023 Feb. Citation on PubMed
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