Potocki-Shaffer Syndrome

Classification according to ICD-10
Q93	Autosome monosomies and deletions, not elsewhere classified
Q93.5	Other deletions of a part of a chromosome
ICD-10 online (WHO version 2019)

The Potocki-Shaffer syndrome ( English Potocki-Shaffer syndrome ) is a very rare genetically caused syndrome in humans that causes various changes in the skeletal system . The cause is a chromosome mutation with deletion of several neighboring genes in section 11p11.2 on chromosome 11 .

Synonyms in the Anglo-American literature are chromosome 11p11.2 deletion syndrome , P11pDS and proximal 11p deletion syndrome .

The disorder as a syndrome was first described in 1996 by L. Potocki and LG Shaffer.

distribution

The frequency ( prevalence ) of the syndrome is given as less than 1: 1,000,000.

By 2006, 23 patients from 14 families had been described. As of October 2012, fewer than 100 cases had been reported.

root cause

Human chromosome 11 idiogram

Emergence

The majority of cases are caused by a deletion of the chromosome segment during the formation of the parental gametes , i.e. sperm or egg cells , or during the early fetal development of the child. It is less common for the person affected to inherit the disorder from a parent. In these cases the disorder follows an autosomal dominant inheritance .

Affected genes

Potocki-Shaffer syndrome is caused by deletion of part of chromosome 11 . On its short arm, proximally (close to the centromere ) is the area 11p11.2 , on which various genes are arranged:

• EXT2 : The loss of this gene causes numerous exostoses . The EXT2 codes for a protein called exostosin-2 , which in turn binds to exostosin-1 in the Golgi apparatus . The complex of exostosin-1 and exostosin-2 influences the formation of heparan sulfate , which is involved in numerous processes in the body.
• ALX4 : The loss of this gene is responsible for the enlarged fontanelles . ALX4 codes for a transcription factor that appears to be important for the normal development of the skull.
• PHF21A codes for BHC80 which, together with BRAF35 and a histone deacetylase, forms the corepressor complex BHC , which in turn is involved in the gene regulation of certain genes for nerve cells .

Presumably, other genes in the same chromosome segment are involved in Potocki-Shaffer syndrome.

Clinical phenomena

The Potocki-Shaffer syndrome is characterized by numerous exostoses , parietal foramina (additional openings in the parietal bone ), enlarged anterior fontanels and occasionally reduced intelligence and developmental delays as well as slight craniofacial anomalies ( malformations of the facial skull ), including short-headedness ( brachycephaly ), pronounced nasal ridge , Shortened distance between nose and mouth (narrow philtrum ), drooping corners of the mouth.

Sometimes there is also a permagna parietal foramina .

The rare symptoms of the syndrome include impaired vision and malformations of the heart , kidneys and other urinary organs .

Very rarely, the exostoses can degenerate into malignant disease, i.e. develop into cancer .

Examination methods and treatment

Diagnosis is clinical (based on symptoms ). The genetic disorder is detected cytogenetically (by means of fluorescence in situ hybridization , FISH test ) or molecular genetic . Occasionally, it is recommended that the parents of an affected child be screened for balanced translocations to assess the risk of recurrence in later children.

It is a systematic search for visual disorders such as strabismus (Strabismus) and nystagmus recommended and after hearing disorders.

The therapy is based on the symptoms and includes elements of early intervention . A causal therapy is not known.

Sources and References

Web links

• Potocki-Shaffer syndrome.  In: Online Mendelian Inheritance in Man . (English)
• Potocki-Shaffer Syndrome. In: Orphanet (Rare Disease Database).
• Potocki-Shaffer syndrome at Genetics Home Reference (ghr.nlm.nih.gov)

Individual evidence

1. ↑ L. Potocki, LG Shaffer: Interstitial deletion of 11 (p11.2p12): a newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2). In: American journal of medical genetics. Volume 62, Number 3, March 1996, pp. 319-325, ISSN  0148-7299 . doi : 10.1002 / (SICI) 1096-8628 (19960329) 62: 3 <319 :: AID-AJMG22> 3.0.CO; 2-M . PMID 8882796 . (Review).
2. ↑ POTOCKI-SHAFFER SYNDROME.  In: Online Mendelian Inheritance in Man . (English)

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