De Grouchy Syndrome
De Grouchy syndrome is the name of two types of chromosomal mutation in humans that can be traced back to losses ( deletions ) of various parts of the short ( 18p- ) or long arm ( 18q- ) of chromosome 18 . Partial monosomies result ; the critical chromosome segment lies in gene location 18q23.
The syndrome is divided into the two types De Grouchy Syndrome I and De Grouchy Syndrome II , which are summarized under the umbrella term deletion syndromes of chromosome 18 . They are each associated with different malformation complexes. A combination of features of both types of syndrome can be seen in people with 18-R syndrome .
The first description from a scientific point of view took place in 1963 and 1964. Since then, more than 100 case studies have been documented.
Symptoms
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The phenotypic expression is very different, by far not all symptoms occur in all affected people, and they can be developed differently from person to person. This presumably (also) depends on the length of the lost piece of the chromosome , although precise connections have not yet been established. Conclusions on the severity of the symptoms and the development of an affected child are therefore not possible. The type and severity of the individual symptoms certainly play an important role in the prognosis . In some cases, the influence of a determined cell mosaic on the severity of the symptoms cannot be ruled out. In such a genetic mosaic, two cell lines exist in parallel , one as usual and one conspicuous (here with the corresponding deletion). Depending on the proportion of normal cells, the symptoms can be milder.
De Grouchy Syndrome I.
Type I of the syndrome is also known by the synonyms 18p syndrome , 18p deletion syndrome , deletion 18p syndrome , del (18p) syndrome , chromosome 18p monosomy , monosomy 18p, and partial monosomy 18p . There is a loss (deletion) of the short arm (18p-) of chromosome 18.
After birth, children are more likely to have a low birth weight and somatic hypotrophy , decreased muscle tension ( hypotonia ), often quite large hands with short fingers, sometimes four- finger furrows , lateral bending of a phalanx ( clinodactyly ) and syndactyly of some toes . Heart defects and intestinal abnormalities ( malrotations ) are possible.
Sometimes some of these and other symptoms are not immediately obvious, but rather develop in the course of the first few years of life. The described features in children with type I of the syndrome include comparatively large ears, sometimes there is a blockage ( atresia ) or narrowing ( stenosis ) of the auditory canals , funnel chest , peculiarities in the area of the brain and head (frequent short-headedness with particular roundness of the head / brachycephaly , holoprosencephaly at one of ten children, some with only one eye / Monophthalmie , absence of the olfactory bulb / Arrhinenzephalie , premature closure of the cranial sutures), special features around the eyes (malformation of the eye muscles / ocular dysmorphia, malformations of the bony eye sockets / orbitare dysmorphia, comparatively small eyes / microphthalmia , eyes that are quite far apart / hypertelorism , unusually narrow eyelid slits / blepharophimosis with the eyelid axis pointing upwards or downwards, crescent-shaped skin folds at the inner corners of the eyes / epicanthus medialis , drooping of one or both upper eyelids ider / ptosis , cataract , glaucoma , coloboma , strabismus / strabismus , eye tremors / nystagmus ), unusually long thumb .
Also described are a significant underdevelopment ( hypoplasia ) and / or a back shift of the lower jaw ( distal bite / mandibular retrognathy ), excessive width of the mouth gap ( macrostomy ), drooping corners of the mouth, peculiarities of the teeth or the tooth development (later tooth eruption , partly missing tooth systems, susceptibility for dental caries ), the presence of a narrowing (stenosis) or an occlusion (atresia) of the choanae , which connect the nasal cavities with the throat , a retarded bone age (thereby slowed growth), spinal column bending ( scoliosis ), hump ( kyphosis ). An inflammation of the thyroid gland ( thyroiditis ), Graves' disease , immune deficiencies with autoimmune symptoms, deficiency in immunoglobulin A , type 1 diabetes mellitus in adolescence and the absence of menstruation ( primary amenorrhea ) in girls .
In the course of child development, a cognitive disability becomes apparent , the degree of which can vary from mild to very severe.
De Grouchy Syndrome II
Type II syndrome has a deletion of the long arm 18q22-23. Here, too, the children stand out due to somatic hypotrophy and, in their further development, due to pituitary- related short stature , probably due to growth hormone insufficiency ( GH insufficiency ). Microcephaly, muscle hypotonia, narrowing or occlusion of the auditory canals, eye malformations, peculiarities of the teeth, cognitive disabilities and immune deficiencies with autoimmune symptoms can occur as with type I.
18-R syndrome
If a child has a ring chromosome 18 with deletion of the long and short arms (r18), combinations of features of De Grouchy syndrome I and II are found.
diagnosis
Chromosome analysis is also the diagnostic tool of choice because the deletion syndromes of chromosome 18 are very rare and the symptoms are variable and therefore difficult to assign . A differential diagnosis , e.g. B. Cerebro-Okulo-Fazio-Skeletal Syndrome can help with the limitation.
treatment
Since it is a chromosomal cause, a causal cure is not possible, so the treatment relates to the symptomatic therapy of individual symptoms.
genetics
The deletion usually consists of a simple loss of a piece on chromosome 18.
In rare cases there is a translocation of chromosome 18 with another chromosome, which arose from an originally reciprocal and balanced form, in which there was an exchange of pieces between two chromosomes or a pericentric inversion without loss of pieces and accordingly without phenotypic effects. People with this balanced chromosome feature are clinically normal and can reproduce. The likelihood of an imbalance in the child's genome during fertilization is possible if the mother or father has a reciprocal translocation or inversion. In the course of the meiosis it can happen with this constellation that both translocation chromosomes are passed on or a so-called crossing over occurs in the inverted section. The previously balanced balance of the genetic makeup is thus disturbed, and pieces are lost, which leads to the respective deletion syndrome in the child.
Repetition probability
In most cases the deletion occurs spontaneously. If the chromosome image ( karyotype ) of both parents is normal or if the affected child has a ring chromosome 18, there is currently no evidence of an increase in the likelihood of conceiving another child with one of the deletion syndromes of chromosome 18.
If the child has a deletion syndrome with translocation or inversion and are visible in the karyotype of the mother or father appropriate balancing problems, increases the likelihood that when procreation is again of another child to a Inbalance of the genome. Parents have the option of receiving human genetic advice before and during pregnancy and of using appropriate prenatal diagnostic procedures to check the presence of a deletion in the child prenatally . Of a positive result and permits them, a termination of pregnancy from a medical indication to have to make.
A clinically normal child whose mother or father has a balanced translocation or inversion may have inherited this and in this case would also be a potential carrier of characteristics.
literature
- W. Andler: Endocrinological disorders in deletions of chromosome 18 (MSchr. Kinderk. 140, 2000, pages 303-306)
- Children's network eV: Information folder on De Grouchy Syndrome
- C. Turleau: Monosomy 18p. In: Orphanet Journal of Rare Diseases. Volume 3, 2008, p. 4, ISSN 1750-1172 . doi : 10.1186 / 1750-1172-3-4 . PMID 18284672 . PMC 2265258 (free full text). (Review).