Wiedemann–Rautenstrauch (WR) syndrome (), also known as neonatal progeroid syndrome, is a rare
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
progeroid syndrome
Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term ''progeroid syndrome'' does not necessarily imply progeria (Hutchinson–Gilford ...
. There have been over 30 cases of WR. WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism.
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
fontanelle
A fontanelle (or fontanel) (colloquially, soft spot) is an anatomical feature of the infant human skull comprising soft membranous gaps ( sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow f ...
s, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (
lipoatrophy), delayed tooth eruption, abnormal hair pattern (
hypotrichosis
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarr ...
), beaked nose, mild to severe intellectual disabilities, and
dysmorphism.
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).
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
Hans-Rudolf Wiedemann (February 16, 1915 - August 4, 2006) was a German pediatrician, University teacher, and autograph collector.
__TOC__ Life
Wiedemann was born in Bremen. His father was a medical practitioner. His mother came from a medical fa ...
in 1979, Devos in 1981 and Rudin in 1988.
References
External links
Progeroid syndromes
Syndromes
Autosomal recessive disorders
Genetic diseases and disorders
Rare diseases
{{genetic-disorder-stub