Wiedemann–Rautenstrauch Syndrome
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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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
progeroid syndrome. 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 Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a Heredity, familial genetic characteristic. People diagnosed with macrocephaly will receive further medical ...
), sparse hair, prominent scalp veins, inward-folded eyelid (
entropion Entropion is a medical condition in which the eyelid (usually the lower lid) folds inward. It is very uncomfortable, as the eyelashes continuously rub against the cornea causing irritation. Entropion is usually caused by Genetics, genetic factors. ...
), 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 ...
s, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (
lipoatrophy Lipoatrophy is the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections of insulin in the treatment of diabetes, from the use of human growth hormone or from subcutaneous injections of copaxone u ...
), 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 scarring ...
), beaked nose, mild to severe intellectual disabilities, and
dysmorphism A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...
.


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 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 134 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...
(10q22.3). This gene encodes the largest subunit (A) of the DNA directed
RNA polymerase III In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize 5S ribosomal RNA, tRNA, and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose ex ...
. This subunit includes the catalytic site of RNA polymerase III. Mutations in this gene have been associated with
hypogonadotropic hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis). Hypothalamic disorders result from a deficiency in the release of gonadotropic ...
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 Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10–12 nm calcium-binding microfibrils. These micro ...
'' that cause a deficiency of the protein hormone asprosin and progeroid-like symptoms with reduced subcutaneous
white adipose tissue White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular Adipocyte, adipocytes. In humans, the healthy body fat percent ...
.


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


External links

{{DEFAULTSORT:Wiedemann-Rautenstrauch syndrome Progeroid syndromes Syndromes Autosomal recessive disorders Genetic syndromes Rare diseases