Wiedemann–Rautenstrauch syndrome

{{Infobox medical condition (new)

| name = Wiedemann–Rautenstrauch syndrome

| synonyms = Neonatal progeroid syndrome

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| caption = This condition is inherited in an autosomal recessive manner.

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Wiedemann–Rautenstrauch (WR) syndrome ({{IPA|de|ˈviːdəman ˈʁaʊtn̩ʃtʁaʊx}}), also known as neonatal progeroid syndrome,{{cite web|title=Wiedemann–Rautenstrauch syndrome|url=http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1104/viewAbstract|work=NORD Rare Disease Report Abstract|access-date=16 March 2013|archive-date=27 March 2013|archive-url=https://web.archive.org/web/20130327115319/http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1104/viewAbstract|url-status=dead}} is a rare autosomal recessive progeroid syndrome. There have been over 30 cases of WR.{{cite web|title=Wiedemann–Rautenstrauch syndrome|url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3455|work=Orphanet|access-date=16 March 2013}} WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism.{{cite journal | vauthors = Arboleda H, Quintero L, Yunis E | title = Wiedemann-Rautenstrauch neonatal progeroid syndrome: report of three new patients | journal = Journal of Medical Genetics | volume = 34 | issue = 5 | pages = 433–437 | date = May 1997 | pmid = 9152846 | pmc = 1050956 | doi = 10.1136/jmg.34.5.433 }}

Presentation

Affected individuals exhibit intrauterine and postnatal growth retardation, leading to short stature and an aged appearance from birth. They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelid (entropion), widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (lipoatrophy), delayed tooth eruption, abnormal hair pattern (hypotrichosis), beaked nose, mild to severe intellectual disabilities, and dysmorphism.{{cite journal | vauthors = Toriello HV | title = Wiedemann-Rautenstrauch syndrome | journal = Journal of Medical Genetics | volume = 27 | issue = 4 | pages = 256–257 | date = April 1990 | pmid = 2325106 | pmc = 1017029 | doi = 10.1136/jmg.27.4.256 }}

Genetics

This condition has been associated with mutations in the POLR3A gene.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 (2018) Bi-allelic POLR3A Loss-of-Function variants cause autosomal-recessive Wiedemann-Rautenstrauch syndrome. Am J Hum Genet This gene is located on the long arm of chromosome 10 (10q22.3).{{Cite web |title=DLX3 distal-less homeobox 3 [Homo sapiens (human)] | work = Gene - National Center for Biotechnology Information (NCBI) |url=https://www.ncbi.nlm.nih.gov/gene/1747 |url-status=live |archive-url=https://web.archive.org/web/20220811044154/https://www.ncbi.nlm.nih.gov/gene/1747 |archive-date=2022-08-11 |access-date=2022-08-11 | publisher = U.S. National Library of Medicine }}

This gene encodes the largest subunit (A) of the DNA directed RNA polymerase III. This subunit includes the catalytic site of RNA polymerase III.{{Cite web |title=POLR2B RNA polymerase II subunit B [Homo sapiens (human)] | work = Gene - National Center for Biotechnology Information (NCBI) |url=https://www.ncbi.nlm.nih.gov/gene/5431 |access-date=2022-08-11 | publisher = U.S. National Library of Medicine }}

Mutations in this gene have been associated with hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia.{{Cite web |title=Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (Concept Id: C3280644) |url=https://www.ncbi.nlm.nih.gov/medgen/482274 |access-date=2022-08-11 | work = MedGen - National Center for Biotechnology Information (NCBI) | publisher = U.S. National Library of Medicine }}{{cite journal | vauthors = Xu W, Plummer L, Quinton R, Swords F, Crowley WF, Seminara SB, Balasubramanian R | title = Hypogonadotropic hypogonadism due to variants in RAB3GAP2: expanding the phenotypic and genotypic spectrum of Martsolf syndrome | journal = Cold Spring Harbor Molecular Case Studies | volume = 6 | issue = 3 | date = June 2020 | pages = a005033 | pmid = 32376645 | pmc = 7304352 | doi = 10.1101/mcs.a005033 | doi-access = free }}

Diagnosis

=Differential diagnosis=

Marfan lipodystrophy syndrome (MFLS) has sometimes been confused with Wiedemann–Rautenstrauch syndrome, since the Marfanoid features are progressive and sometimes incomplete.{{cite journal | vauthors = Jacquinet A, Verloes A, Callewaert B, Coremans C, Coucke P, de Paepe A, Kornak U, Lebrun F, Lombet J, Piérard GE, Robinson PN, Symoens S, Van Maldergem L, Debray FG | display-authors = 6 | title = Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene | journal = European Journal of Medical Genetics | volume = 57 | issue = 5 | pages = 230–234 | date = April 2014 | pmid = 24613577 | doi = 10.1016/j.ejmg.2014.02.012 }}

MFLS is caused by mutations near the 3'-terminus of FBN1 that cause a deficiency of the protein hormone asprosin and progeroid-like symptoms with reduced subcutaneous white adipose tissue.{{Cite web|url=http://www.omim.org/entry/616914|title=OMIM Entry - #616914 - Marfan Lipodystrophy Syndrome; MFLS|work = Online Mendelian Inheritance in Man (OMIM) |access-date=2016-12-06}}

History

WR was first reported by Rautenstrauch and Snigula in 1977,{{cite journal | vauthors = Rautenstrauch T, Snigula F | title = Progeria: a cell culture study and clinical report of familial incidence | journal = European Journal of Pediatrics | volume = 124 | issue = 2 | pages = 101–111 | date = January 1977 | pmid = 319005 | doi = 10.1007/BF00477545 | s2cid = 19472544 }} and the earliest reports made subsequently have been by Hans-Rudolf Wiedemann in 1979,{{cite journal | vauthors = Wiedemann HR | title = An unidentified neonatal progeroid syndrome: follow-up report | journal = European Journal of Pediatrics | volume = 130 | issue = 1 | pages = 65–70 | date = January 1979 | pmid = 569581 | doi = 10.1007/BF00441901 | s2cid = 22966149 }} Devos in 1981{{cite journal | vauthors = Devos EA, Leroy JG, Frijns JP, Van den Berghe H | title = The Wiedemann-Rautenstrauch or neonatal progeroid syndrome. Report of a patient with consanguineous parents | journal = European Journal of Pediatrics | volume = 136 | issue = 3 | pages = 245–248 | date = July 1981 | pmid = 7262096 | doi = 10.1007/BF00442991 | s2cid = 39122445 }} and Rudin in 1988.{{cite journal | vauthors = Rudin C, Thommen L, Fliegel C, Steinmann B, Bühler U | title = The neonatal pseudo-hydrocephalic progeroid syndrome (Wiedemann-Rautenstrauch). Report of a new patient and review of the literature | journal = European Journal of Pediatrics | volume = 147 | issue = 4 | pages = 433–438 | date = May 1988 | pmid = 3294017 | doi = 10.1007/BF00496430 | s2cid = 6557563 }}