Stromme syndrome: symptoms, causes and treatments

It is one of the rarest known syndromes of genetic origin: it affects very few people.

Have you ever heard of Stromme syndrome? It is a very rare genetic condition, autosomal (appearing on non-sex chromosomes) and recessive (implying that both genes in a pair must be mutated to produce the disease).

This syndrome mainly affects the intestine, although it also affects many other structures and systems (cardiac, skeletal, neurological...).

In this article we will know its most relevant characteristics, its symptoms, causes and possible treatments to apply.

What is Stromme syndrome?

The Stromme Syndrome (in English, Strømme syndrome) is an autosomal recessive genetic syndrome, considered rare, that primarily affects the intestine.. It produces intestinal atresia, which leads to certain congenital malformations in the structure of the intestine (such as the lack of a part of it), causing intestinal obstruction.

In the case of Stromme Syndrome, the intestinal atresia is characterized as "apple peel", meaning that the remaining intestine is twisted around its main artery..

In addition to these bowel malformations, two other key symptoms also appear in Stromme syndrome: ocular anomalies and microcephaly..

Recall that microcephaly is a medical condition that involves the brain not developing properly in the baby, so the head is smaller than normal; microcephaly can appear at birth, or develop during the first years of life.

In Stromme syndrome, the front third of the eye (also called the anterior segment or inner socket), which encompasses certain structures of the eye (cornea, iris, ciliary body and lens) is underdeveloped. In addition, the syndrome is characterized by moderate developmental delay.

These are the most typical symptoms of Stromme syndrome, although other, somewhat less frequent symptoms also occur. One of them is atrial septal defect (also called ASD), which is a congenital heart defect. congenital heart disease where Blood flows between the atria of the heart..

In addition, in people with Stromme syndrome, muscle tone is increased, and skeletal abnormalities are often present. Sometimes other conditions appear, for example intellectual disability, poor speech, poor motor function, or other symptoms. or other symptoms.

Prevalence

Stromme syndrome is a very rare conditionalthough its prevalence data are still unknown. It is known, however, that in 2017 approximately 13 people were diagnosed with it.

Origin

It was Petter Strømme, a Norwegian pediatrician, together with his teamwho identified the symptoms of Stromme syndrome for the first time in 1993 (as we can see, its name derives from its "discoverer").

Strømme and his collaborators observed the symptoms of the syndrome in two siblings, although it was not until 2008 that the syndrome was named for the first time, in a study with another patient. Later, in 2015, the pathogenic mutations produced in the CENPF gene, and which characterize Stromme syndrome, could be precisely identified.

Just one year later from that date, in 2016, it was discovered, in siblings who had manifested symptoms in 1993, mutations in the CENPF gene gene (in the two copies of the gene), through a genetic study. It was thus possible to identify these mutations in the gene as the cause of Stromme Syndrome.

Symptoms

We have seen in a generic way what are the most characteristic symptoms of Stromme syndrome; we will now see them one by one and in more detail.

Intestinal atresia

The intestinal atresia that characterizes the Stromme syndrome consists of the absence of certain parts of the intestine, or the narrowing of the intestine.. This implies an intestinal obstruction, which requires an operation.

2. Ocular abnormalities

The eyes are usually smaller than normal, as well as being underdeveloped (this is more often seen in one eye than in the other). (moreover, this is usually seen more in one eye than the other).

The alterations that may appear are: coloboma in the iris (a kind of hole), cataracts, sclerocornea (the cornea blends with the white of the eye), leukoma (opacity of the cornea), microcornea (small cornea)...

3. Microcephaly

As we have already seen, microcephaly implies that the brain develops abnormally, which implies a smaller head than usual. Associated with it may also appear intellectual disability, seizures, dwarfism, motor disturbances...

4. Moderate developmental delay

Generally the developmental delay is usually moderate to severe, although there are cases where it is mild.

5. Atrial septal defect

The heart may also be affected in Stromme syndrome, through a congenital heart defect called atrial septal defect, which involves blood flowing between the atria of the heart.

6. Increased muscle tone

Also called hypertoniaincreased muscle tone is another sign of Stromme syndrome.

7. Skeletal abnormalities

The skeletal system is also altered through various anomalies, such as: hip dysplasia (which may result in dislocation), metopic craniosynostosis, flattened vertebraemalformations in the thoracic wall (which receives the name of sternal cleft), etc.

8. Physical characteristics (phenotype)

At the physical level (i.e. phenotype), people with Stromme syndrome are usually short, short in stature, with a short stature and a short stature. are usually short in stature, with large, low-set ears, large mouth and small jaw, thin or sparse hair, and a small number of hairs.They have thin or sparse hair and epicanthal folds (which are folds of the skin of the upper eyelid, which cause the inner corner of the eye to be covered).

Causes

As we have seen, Stromme syndrome is a genetic condition. It is caused by a series of mutations in both copies of a gene called CENPF; this gene encodes the centromere F protein, which is involved in cell division processes.

On the other hand, CENPF gene is linked to processes of cell division, migration and differentiation.What happens when this gene is mutated (mutations appear in it)? Cell division is slower, and in addition, certain processes of embryonic development are interrupted or incomplete.

How is Stromme syndrome diagnosed? Generally, a clinical diagnosis is made, that is to say, based on the symptoms, although logically genetic tests are the ones that will confirm the diagnosis, in addition to providing much more complete information.

Treatment

As for the treatment of Stromme syndrome, it is mainly focused on the symptoms (each of them will need its own specific treatment). At the level of the intestine, and to treat intestinal atresia, the malformation is surgically corrected, usually in infancy.usually in infancy.

Specifically, a surgical anastomosis is performed, a technique used to incorporate a new connection between two fluid-carrying structures of the body (in this case, the intestines).

Prognosis

As for the prognosis of this syndrome, it is still unclear. Most people with Stromme syndrome survive birth and infancy.Although there is a part of the cases (a minority), which are more severe and do not survive (or die before birth, or shortly after).

Bibliographical references:

• Dorum, B.A., Şambel, I.T., Özkan, H., Kırıştıoğlu, I., Köksal, N. (2017). Stromme syndrome: new clinical features . APSP Journal of Case Reports . 8 (2): 14.
• Filges, I., Bruder, E., Brandal, K., Meier, S., Undlien, DE, Waage, TR, Hoesli, I., Schubach, M., de Beer, T., Sheng, Y., Hoeller , S., Schulzke, S., Rosby, O., Miny, P., Tercanli, S., Oppedal, T., Meyer, P., Selmer, KK, Stromme, P. (2016). Stromme syndrome is a ciliary disorder caused by mutations in CENPF. Hum. Mutat, 37: 359-363.
• Filges, I., Stromme, P. (2019). CUGC for Stromme syndrome and CENPF-related disorders. European Journal of Human Genetics : 1-5.
• Slee, J., Goldblatt, J. (1996). Further evidence for an 'apple peel' intestinal atresia syndrome, ocular anomalies and microcephaly. Clin. Genet, 50: 260-262.
• Strømme, P ., Dahl, E ., Flage, T ., Stene-Johansen, H. (1993). Intestinal apple peel atresia in siblings with ocular anomalies and microcephaly. Clinical Genetics . 44 (4): 208-210.