Okihiro syndrome

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The Duane-radial ray syndrome - also known as (Engl.) Duane Radial Ray syndrome (DRRS) called - is an autosomal - dominant inherited combination of malformations .

Symptoms

Characteristic are malformations of the upper limbs (almost identical to those in Holt-Oram syndrome ) in combination with a Duane anomaly , a special form of squint in which one cannot see outward. The limb malformations affect the thumbs (tripartite thumbs, underdeveloped (hypoplastic) thumbs, but in contrast to Holt-Oram syndrome also excess thumbs (preaxial polydactyly)) and usually occur together with malformations of the radius (spoke). The arms can also be shortened to a phocomelia .

In addition, there are often kidney malformations and / or an incorrect position of the kidneys. Hearing disorders were initially described as characteristic, but are only found in around 19% of those affected. Ear malformations and foot malformations occur. Heart defects are also not uncommon, here atrial septal and more often ventricular septal defects. Some children with Okihiro syndrome are short due to a lack of growth hormone. Occasionally there are facial asymmetries. Also anal atresia may occur.

The syndrome occurs comparatively rarely, the average probability of occurrence is a maximum of 1: 100,000. in the majority of cases it arises sporadically due to a new mutation (no figures are available here so far).

root cause

Cause of Okihiro syndrome, genetic mutations in the gene (genetic disposition) SALL4 (SAL-like protein 4) on chromosome 20 locus q13.13-13.2 that are found at about 90 to 95% of people with the syndrome.

The Okihiro syndrome can with a thalidomide - embryopathy be confused (thalidomide syndrome), since both syndromes in the complete loss of the transcription factor is based of the gene SALL4 and like malformations have. Naturally occurring mutations are the cause of Okihiro syndrome. In thalidomide syndrome, various transcription factors are broken down on a broad basis, including that of the SALL4 gene.

Due to the same damage pattern, a mutagenic effect of thalidomide was initially assumed. However, this is not the case, as the SALL4 gene is unchanged in people with Contergan Syndrome. By demonstrating genetic defects in the SALL4 gene in people with Okihiro syndrome, it was possible to show that their malformations are not due to the ingestion of thalidomide.

It is important to distinguish it from the Holt-Oram syndrome (caused by peculiarities in the TBX5 gene on chromosome 12 ). The same arm malformations (with the exception of the surplus thumbs, which are extremely rare - if at all - in Holt-Oram syndrome) and heart defects are present here. About 80% of people with Holt-Oram syndrome have arrhythmias that are not known to be associated with Okihiro syndrome. If there are other malformations in addition to the heart and limb malformations, Holt-Oram syndrome is almost impossible.

Okihiro syndrome can also be confused with Townes-Brocks syndrome , which is caused by defects in the similar gene SALL1 on chromosome 16 . The syndrome is characterized by ear malformations, thumb malformations (as in Okihiro syndrome) and anal atresia. The radius is not shortened in this syndrome. However, in Townes-Brocks syndrome, a Duane anomaly can rarely be present.

Other peculiarities with very similar symptoms are thrombocytopenia absent radius syndrome ( TAR syndrome ) (here the thumbs are always preserved, but the radius is always missing and the platelet count is lower than usual) and Fanconi anemia (here is a special brittleness of the chromosomes and a tendency to tumor).

forecast

The life expectancy of people with Okihiro syndrome is generally not reduced. The correction of the usually mild heart defect as well as correction of the malformations of the extremities and strabismus operations to treat the Duane anomaly are therapeutically important . Kidney function must be monitored, but kidney dysfunction is rare. If Okihiro syndrome is suspected, a hearing test should be done at an early stage.

Web links

Individual evidence

  1. ^ Contergan: cause of malformations found. Ärzteblatt, August 3, 2018, accessed August 4, 2018 .
  2. ↑ Katherine A Donovan et al .: Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray Syndrome. elifesciences.org, August 1, 2018, accessed August 4, 2018 .