Wiedemann–Rautenstrauch syndrome

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.

Genetics

This condition has been associated with mutations in the POLR3A gene. This gene is located on the long arm of chromosome 10 (10q22.3).

This gene encodes the largest subunit (A) of the DNA directed RNA polymerase III. This subunit includes the catalytic site of RNA polymerase III.

Mutations in this gene have been associated with hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia.

Diagnosis

Differential diagnosis

Marfan lipodystrophy syndrome (MFLS) has sometimes been confused with Wiedemann–Rautenstrauch syndrome, since the Marfanoid features are progressive and sometimes incomplete.

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.

History

WR was first reported by Rautenstrauch and Snigula in 1977, and the earliest reports made subsequently have been by Hans-Rudolf Wiedemann in 1979, Devos in 1981 and Rudin in 1988.

References

References

1. "Wiedemann–Rautenstrauch syndrome". NORD Rare Disease Report Abstract.
2. "Wiedemann–Rautenstrauch syndrome". Orphanet.
3. (May 1997). "Wiedemann-Rautenstrauch neonatal progeroid syndrome: report of three new patients". Journal of Medical Genetics.
4. (April 1990). "Wiedemann-Rautenstrauch syndrome". Journal of Medical Genetics.
5. 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
6. "DLX3 distal-less homeobox 3 [Homo sapiens (human)]". U.S. National Library of Medicine.
7. "POLR2B RNA polymerase II subunit B [Homo sapiens (human)]". U.S. National Library of Medicine.
8. "Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (Concept Id: C3280644)". U.S. National Library of Medicine.
9. (June 2020). "Hypogonadotropic hypogonadism due to variants in ''RAB3GAP2'': expanding the phenotypic and genotypic spectrum of Martsolf syndrome". Cold Spring Harbor Molecular Case Studies.
10. (April 2014). "Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene". European Journal of Medical Genetics.
11. "OMIM Entry - #616914 - Marfan Lipodystrophy Syndrome; MFLS". Online Mendelian Inheritance in Man (OMIM).
12. (January 1977). "Progeria: a cell culture study and clinical report of familial incidence". European Journal of Pediatrics.
13. (January 1979). "An unidentified neonatal progeroid syndrome: follow-up report". European Journal of Pediatrics.
14. (July 1981). "The Wiedemann-Rautenstrauch or neonatal progeroid syndrome. Report of a patient with consanguineous parents". European Journal of Pediatrics.
15. (May 1988). "The neonatal pseudo-hydrocephalic progeroid syndrome (Wiedemann-Rautenstrauch). Report of a new patient and review of the literature". European Journal of Pediatrics.