Monday, June 1, 2009

Ok Chromosome Abnormalities


First I will tell you all the info I have on Full (in all cell's) Partial(only part of the chromosome not all)8 Trisomy.

A little back ground on my family first:
I have 4 boys the youngest the oldest and Sonya didn't have this extra part of a chromosome. My two middle boys do have this extra piece of 8.

Ok so how we found out about this is Collin and Bryan have always had delays but teachers and doctors assured us that since they hit all there earlier milestones with in the spectrum of normal that these delays were more then likely emotional so we treated it as such giving the early help as soon as problems a rised and putting them in ppi so they could get the extra help they needed and thought that was that it was helping so we kept doing what we were doing.

So after some time we (parents and teachers) noticed Bryan was having tremors in his hands when he was doing fine motor skills and were concerned about it.So I took him to his ped and he referred us to a peds neurologist.We went to the neurologist and they said it was a hereditary tremor and there is nothing that can be done about it but they wanted to do blood work to check for chromosome abnormality.

About 2 weeks later they call and tell us he has a marker chromosome and they don't know what chromosome it is from or if it is the cause of his delays so they need him to come in for more tests to see.

So we brought Collin and Bryan in and they tested them and realized they both have an extra piece of the middle of the 8h chromosome in all cells and that it more then likely was the cause of there delays but not what caused Bryan's Tremors . We also found out that I have this same in about 75 percent of mine. We had Joey and Logan tested after Logan was born and they didn't have it.

So the Gene Counselor didn't know much about it so I did my own research and this is what I have found out about it:

Chromosome 8, partial trisomy is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Chromosome 8, partial trisomy, or a subtype of Chromosome 8, partial trisomy, affects less than 200,000 people in the US population.
I can not remember where I found this.

Marker Chromosome:
A marker chromosome (mar) is a structurally abnormal chromosome in which no part can be identified. The significance of a marker is very variable as it depends on what material is contained within the marker.

It is essentially a partial trisomy. However sometimes the marker is composed of inactive genetic material and has little or no effect. There are some markers that are passed down through a family with little effect. There are some markers that arise as new events. Often, markers are not passed down as they can be lost during cell division due to their small size. There are some individuals who have multiple markers. When special studies are performed to identify the material more conclusions can be drawn about the effects of the marker. There is a more common marker called inverted duplication of chromosome 15. This is a specific syndrome that has developmental delays and physical variations and often seizures as its features. A difficult situation arises when a marker chromosome is found on a prenatal study such as amniocentesis. If the marker is not one of the more common markers and neither parent has the marker, it can be very difficult to predict the effects of the marker. Usually, if a parent carries the same marker, the effect is much less.

I found this at: Wikipedia


And this which is so much like my boys:
Titre du document / Document title
Familial transmission of a small supernumerary marker chromosome 8 identified by FISH : An update
Auteur(s) / Author(s)
ROTHENMUND H. (1) ; CHUDLEY A. E. (1 2) ; DAWSON A. J. (1 2) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Human Genetics, University of Manitoba, Winnipeg, Manitoba, CANADA
(2) Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, CANADA
Résumé / Abstract
A father and his 2 daughters were previously determined to carry a small, supernumary marker chromosome [Chudley et al., 1983]. The origin of this marker could not be determined by standard cytogenetic techniques. In this study, fluorescence in situ hybridization (FISH) studies identified the marker chromosome as a pericentric derivative of chromosome 8.(Like Me) The father has low grade mosaicism for this marker and is phenotypically normal.(Like My Boys) Both daughters are non-mosaic and show developmental delays and somewhat differing clinical findings. The phenotypes of the 2 sisters are compared with those previously reported for supernumerary der(8) patients. This is the first report of familial transmission of a supernumerary der(8) marker chromosome.

Info From: Here


Not much you say? Yeah that's what I thought to! I couldn't find much but I am hoping it is studied more in the future so we can learn more.

On to Sonya.

Sonya died in my 17th week of pregnancy the day before she would have been in the 18th week. We had test run to find out she her 21 chromosome translocatied to the other one and then deleted. I the doctor told me she should not have lived as long as she did and they have no idea but for the grace of god why she did. She said she only has heard of 9 cases of this ever and so I researched and didn't find much but this is what I did find:

Monosomy is a form of aneuploidy with the presence of only one chromosome (instead of the typical two in humans) from a pair.[1] Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies.

From:Here

Only nine cases of monosomy 21 have been described to our knowledge. Six of them were liveborn and three were from spontaneous abortions. As many of the reports were from the late 1970's or early 1980's when banding techniques were not generally of as high quality as is currently possible, it may be that some of the reports were not in fact true monosomy 21 (i.e. a piece of 21 could have been translocated to a larger chromosome). Only the cases of Joosten et al. and Ma et al. were confirmed molecularly. In the former case, monosomy 21 was prenatally diagnosed in chorionic villi using fluorescent in situ hybridization (FISH), while in the latter, monosomy 21 was observed in a spontaneous abortion from a pregnancy conceived by ICSI. DNA investigations in both cases revealed a paternal origin of the single chromosome 21. Full monosomy 21 in a liveborn may be impossible without being associated with mosaicism.

Petersen et al. (1992) (also Bartsch et al, 1994) reported two interesting cases of mosaicism involving monosomy 21 cells, cells with abnormal chromosomes 21 and cells with uniparental disomy for chromosome 21. In both cases it appears the abnormal chromosome 21 was lost from some cells then replaced with a copy of the 'normal' chromosome 21.

From:Here


Symptoms of Chromosome 21 monosomy

Chromosome 21 monosomy: A rare chromosomal disorder where there is only one copy of chromosome 21 instead of the normal two leading to various abnormalities.

The list of signs and symptoms mentioned in various sources for Chromosome 21 monosomy includes the 62 symptoms listed below:

* Dysmorphic face
* Asymmetric face
* Small head
* Small jaw
* Prominent forehead
* Low set ears
* Malformed ears
* Large pinnae
* Down slanting space between eyelids
* Widely spaced eyes
* Telecanthus
* Anterior eye chamber defects
* Coloboma
* Optic atrophy
* Large nose
* Broad nose
* Long philtrum
* Epicanthal folds
* Large mouth
* Down turned corners of mouth
* Highly arched palate
* Cleft lip
* Cleft palate
* Delayed dentition
* Abnormal tooth roots
* Abnormal tooth crowns
* Short neck
* Short thorax
* Narrow pelvis
* Small hands
* Small feet
* Overlapping fingers
* Overlapping toes
* Flexed fingers
* Flexed toes
* Syndactyly of toes
* Clinodactyly
* Clubfoot
* Arthrogryposis
* Kyphosis
* Scoliosis
* Excessive muscle tone
* Reduced muscle tone
* Seizures
* Spastic paresis
* Hyperactive reflexes
* Brain abnormalities
* Brain atrophy
* Dilated brain ventricles
* Small cerebrum
* Small cerebellum
* Respiratory distress
* Imperforate anus
* Kidney agenesis
* Micropenis
* Hypospadias
* Undescended testes
* Growth retardation
* Motor retardation
* Mental retardation
* Failure to thrive
* Death usually before birth or by 20 months

Not nice huh?I was heart broken knowing my daughter had some or all this wrong with her!My poor poor Sonya Marie! I love her but know now she is perfect playing running and happy in a better place with no more pain or fear to feel!

This is from:Here

PubMed articles by:
Vorsanova, S.
Iourov, I.
Voinova-Ulas, V.
Liehr, T.


Mol Cytogenet. 2008; 1: 13.
Published online 2008 June 19. doi: 10.1186/1755-8166-1-13.

PMCID: PMC2442098
Copyright © 2008 Vorsanova et al; licensee BioMed Central Ltd.
Partial monosomy 7q34-qter and 21pter-q22.13 due to cryptic unbalanced translocation t(7;21) but not monosomy of the whole chromosome 21: a case report plus review of the literature
Svetlana G Vorsanova,1,2 Ivan Y Iourov,1,2 Victoria Y Voinova-Ulas,1 Anja Weise,3 Victor V Monakhov,2 Alexei D Kolotii,1 Ilia V Soloviev,2 Petr V Novikov,1 Yuri B Yurov,1,2 and Thomas Liehrcorresponding author3
1Institute of Pediatrics and Children Surgery, Roszdrav, Moscow, Russia
2National Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia
3Institute of Human Genetics and Anthropology, Friedrich Schiller University, Jena, Germany
corresponding authorCorresponding author.
Svetlana G Vorsanova: svorsanova@mail.ru; Ivan Y Iourov: ivan_iourov@yahoo.com; Victoria Y Voinova-Ulas: vulas@pedklin.ru; Anja Weise: aweise@mti.uni-jena.de; Victor V Monakhov: y_yurov@yahoo.com; Alexei D Kolotii: svorsanova@mail.ru; Ilia V Soloviev: ivan_iourov@yahoo.com; Petr V Novikov: vulas@pedklin.ru; Yuri B Yurov: y_yurov@yahoo.com; Thomas Liehr: i8lith@mti.uni-jena.de
Received December 4, 2007; Accepted June 19, 2008.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background
Autosomal monosomies in human are generally suggested to be incompatible with life; however, there is quite a number of cytogenetic reports describing full monosomy of one chromosome 21 in live born children. Here, we report a cytogenetically similar case associated with congenital malformation including mental retardation, motor development delay, craniofacial dysmorphism and skeletal abnormalities.
Results
Initially, a full monosomy of chromosome 21 was suspected as only 45 chromosomes were present. However, molecular cytogenetics revealed a de novo unbalanced translocation with a der(7)t(7;21). It turned out that the translocated part of chromosome 21 produced GTG-banding patterns similar to original ones of chromosome 7. The final karyotype was described as 45,XX,der(7)t(7;21)(q34;q22.13),-21. As a meta analysis revealed that clusters of the olfactory receptor gene family (ORF) are located in these breakpoint regions, an involvement of OFR in the rearrangement formation is discussed here.
Conclusion
The described clinical phenotype is comparable to previously described cases with ring chromosome 21, and a number of cases with del(7)(q34). Thus, at least a certain percentage, if not all full monosomy of chromosome 21 in live-borns are cases of unbalanced translocations involving chromosome 21.

Background
Non-mosaic monosomy of chromosome 21 is suggested to be incompatible with life as such cases have been occasionally detected in spontaneous abortions [1-3]. To our knowledge there was only one report on full monosomy 21 diagnosed prenatally with a delivery of a male newborn with multiple congenital malformations who has not survived beyond the first day of life [4]. Moreover, the only monosomy potentially viable in humans seems to be that of the X-chromosome [5]. However, in the literature, a number of cytogenetic reports concerning 'full monosomy of chromosome 21' in live-born children can be found. These contradictory findings usually are explained by undetected mosaicism including a normal cell line in different tissues, or are attributed to unbalanced translocations appearing as the loss of chromosome 21 [6].
Here, we describe a case of a female patient with multiple congenital malformations referred to as a non-mosaic monosomy of chromosome 21 after GTG-banding, which, after application of molecular cytogenetic techniques, turned out to be the first case with an unbalanced translocation of chromosomes 7 and 21.

Results
Case presentation
The patient, a 2 1/2-years-old girl suffering from mental retardation, motor development delay, craniofacial dysmorphism and skeletal abnormalities, was the first child of non-consanguineous parents, born in 40th week gestation. Both in mother (24 years) and in father (35 years) had no family history of mental retardation or developmental delay. A paternal grandmother has experienced a pregnancy resulted in a male stillbirth at 28 weeks of gestation.
The pregnancy was associated with intrauterine growth retardation. The newborn was hypoplastic with a birth weight of 1830 g (<3. centile), a birth length of 44 cm (<3. centile) and occipitofrontal head circumference (OFC) of 30 cm (<3. centile). At birth, facial dysmorphism, large dysplastic ears, arachnodactyly and congenital scoliosis were noticed. Mental and motor developments were retarded. Specific developmental milestones were delayed: turning did not occur until 13th month and free sitting until 19th months of age. Supported walking started at 2 1/2 years. Speech development was not achieved despite unaffected hearing function as to audiometric investigations. Clinical examination at the age of 2 1/2 years showed length 90 cm (50. centile), weight 11 kg (5 centile). Severe microcephaly with OFC 43 cm (<3. centile) and profound mental retardation were obvious. Furthermore, urinary and intestinal incontinence was revealed. Muscular hypotonia was marked. Craniofacial dysmorphisms manifested as microbrachycephaly, hypotelorism, short and upslanted palpebral fissures, broad nasal tip, micrognathia, large dysmorphic ears, and long philtrum. Curly scalp hair despite straight hair in parents was noticed. She had short neck, arachnodactyly, transverse palmar crease, partial cutaneous syndactily of the second and third toes, pectus excavatum and scoliosis (Figs. 1A, 1B, 1C, 1D, 1E). Ophthalmologic examination revealed hypermetropia of high degree and strabismus convergens alternans. Echocardiography showed mitral valve prolapse. Ultrasonography of kidneys revealed double renal pelvis. X-ray detected abnormality of lumbar spine resulting in lateral curvature of spinal column (Fig. 1F). Atrophy of prefrontal cortex and dilatation of lateral and third ventricles were found on magnetic resonance imaging of the brain (T1 and T2 weighting).
Figure 1 Figure 1
(A) Facial appearance of reported patient. (B) pectus excavatum. (C) partial cutaneous syndactily of the second and third toes. (D) transverse palmar crease. (E) scoliosis. (F) Abnormality of lumbar spine (additional cone-shaped hemivertebra between II (more ...)
Cytogenetics
Cytogenetic analysis revealed an abnormal female karyotype demonstrating the lack of one of homologous chromosome 21 in all the 40 metaphase spreads examined. Even though possible changes of banding patterns within the proximal part of long arm of one of homologous chromosome 7 were assumed (Fig. 2A) the GTG-banding analysis was found not to be sufficient enough to come to a final conclusion. In order to clarify whether the reported case was associated with a translocation involving chromosomes 7 and 21, a series of fluorescence in situ hybridization (FISH) experiments were carried out. First, FISH using whole chromosome painting probes (WCP) for chromosomes 7 and 21 were applied. The analysis revealed an imbalanced translocation event involving chromosomes 7 and 21 in all 100 metaphases spreads examined (Fig. 2B). This rearrangement was further characterized by multicolor banding (MCB) for chromosome 21 [7]. The analysis revealed the loss of 21pter-q22.13 due to unbalanced translocation t(7;21) (Fig. 2C). In order to assess the size of the loss within 7q and to define the exact size of the monosomy of 21q, FISH experiments with centromeric and site-specific DNA probes (Table 1; Fig. 3) were performed. Taking into account the data of molecular cytogenetic studies the chromosome abnormality was concluded to be partial monosomy 7q34-qter and 21pter-q22.13 due to an unbalanced translocation t(7;21). Thus, the karyotype was established as 45,XX,der(7)t(7;21)(q34;q22.13),-21. The GTG banded karyotyping and FISH using WCP7 and WCP21 probes showed that the parents had normal karyotypes. Therefore, chromosome abnormality detected was defined as de novo.
Figure 2 Figure 2
(A) GTG-banding appearance of chromosomes 7, note the similarity of banding patterns. (B) FISH with whole chromosome painting (WCP) probes for chromosomes 7 (green) and 21 (red) showed a translocation involving these chromosomes. (C) Multicolor banding (more ...)
Table 1 Table 1
Summary of FISH studies using site-specific DNA probes.
Figure 3 Figure 3
FISH with D13Z1/D21Z1 (A) and MCG-P-2C-01 (B) probes (for more details see also

Discussion
Despite major developments in cytogenetic techniques made throughout last three decades, routine diagnosis using standard GTG banded karyotyping is still facing cases with unexpected findings [3,6]. A chromosomal abnormality initially diagnosed as a 'full monosomy of chromosome 21' is one of those and the suggested fetal lethality of monosomy 21 is then the indication for further cytogenetic investigations of such cases [6].
One unique description of a comprehensively investigated live born child with presumably non-mosaic monosomy 21 had demonstrated the loss of chromosome 21 to produce exceedingly severe congenital malformations incompatible with life and defined monosomy 21 as an extremely rare chromosome abnormality in live born [4]. Moreover, reviewing the literature indicated that no fewer than 9 cases of unbalanced translocation involving chromosome 21 identified by FISH or molecular genetic studies of initially diagnosed 'full monosomy 21' were reported. Among them, five cases were re-diagnosed as t(5p;21q), two cases as t(11;21)(q24;q22.2), and one case, each, as t(4q;21q), t(18q;21q), and t(X;21), respectively [8-16]. Additionally, a case of low-level mosaic trisomy 21 in an individual with fragile × syndrome was reported [17]. Thus, up to now, no similar cases involving chromosome 7 and 21 were described.
The majority of cases reported were de novo unbalanced translocations [8,10,11,14,15], suggesting the formation of such chromosome abnormalities being due to a reciprocal translocation involving chromosome 21 followed by the loss of one of the derivative chromosomes, regardless having an active centromere. As the phenotypic manifestations of these cases are variable, the clinical picture is more likely to be determined by the loss of other chromosome regions except those of chromosome 21.
Unfortunately, the exact breakpoints were not detailed for almost all of the aforementioned previously reported cases with cryptic translocations involving chromosome 21. In our case, the breakpoints were determined to be in 7q34 and 21q22.13. Interestingly, a check of these breakpoint regions in the NCBI build 36.1 database revealed that clusters of the olfactory receptor gene family (ORF) are located in these two regions (Fig. 4). It is known that these ORF regions can be involved in unequal crossing over and promote translocations between different regions of the genome [18]. Thus, an involvement of OFR in the formation of the rearrangement of at least the reported case and probably in other 'cryptic full monosomy 21 cases' cannot be neglected and should be clarified in further studies.
Figure 4 Figure 4
Analysis of breakpoint regions of the index case in the NCBI build 36.1 database depicting the clusters of the olfactory receptor gene family (ORF) to be located in these two chromosomal regions.
As the proximal part of chromosome 21 is known to carry less genes than chromosome 7qter, it was reasonable to suggest that main clinical features of the reported case could be similar to those described previously in cases with del(7)(q34) [6]. In accordance with these considerations, actually a number of phenotypic features such as renal abnormalities, microcephaly, atrophy of prefrontal cortex, short neck, 2/3 syndactyly of toes and multiple minor anomalies including epicanthic folds, upstanding palpebral fissures, low-set ears corresponded to previous clinical data on cases with del(7)(q34). Nonetheless, the phenotypic appearance was found also surprisingly similar to a previously described case of ring chromosome 21 [19]. Common features of r(21) and present case were characteristic craniofacial dysmorphism (microbrachycephaly, hypotelorism, short and upslanted palpebral fissures, broad nasal tip, micrognathia, large dysmorphic ears, and long philtrum) and curly scalp hair. Thus, the contribution of 21q loss may be significant for the clinical findings, as well. However, common phenotypic features of chromosome abnormalities as mental retardation, motor development delay and intrauterine growth retardation are most likely to refer to the combined effect of simultaneous loss of both 7q and 21q.

Conclusion
Since the appearance of G-banded derivate chromosome may be similar to the original GTG banding as it was the case of chromosome 7 in the present case report, molecular cytogenetic techniques represent the most convenient way to prove or refute initial diagnosis. Thus, when analyzing cases that appear to be a 'full monosomy of chromosome 21' or partial monosomy of chromosome 21 due to unbalanced translocations, the application of high resolution molecular cytogenetic techniques (e.g. multi-probe FISH, MCB, or CGH) is unavoidable. Although the latter may appear evident, further cases of unbalanced translocations involving chromosome 21 seems to be required in order to improve subsequent clinical and cytogenetic diagnosis of cases suggested to be a case of monosomy involving the proximal gene-poor region of the chromosome 21 with the precision of breakpoints location

Methods
Cytogenetics
Peripheral blood samples of the patient and her parents were cultivated, harvested and GTG-banded according to standard cytogenetic protocols [20].
DNA probes
FISH experiments were carried out using whole chromosome painting probes (WCP) for chromosomes 7 and 21 [21] and multicolor banding (MCB) for chromosome 21 [7]. Additionally, two-color-FISH experiments were done using the probes specified in Table 1, which are included in the original collection of laboratory of cytogenetics of National Research Center of Mental Health RAMS [22-24] (for details see also Table 1).
FISH
FISH was performed according to previously described protocols [21-24]. Multicolor banding (MCB) was generated on methaphase chromosomes as detailed earlier [7].
Statement
The research done here was carried out in compliance with the Helsinki Declaration – the ethical committee of the National Research Center of Mental Health (RAMS), Moscow approved the study.

Authors' contributions
SGV participated in the design of the study, analyzed clinical and cytogenetic data, and drafted basically the manuscript, IY I participated in the design of the study, drafted basically the manuscript and evaluated the FISH-studies, VY V-U picked up the case and was involved in the clinical studies and description, A W performed, evaluated and interpreted the sophisticated molecularcytogenetic studies (MCB-studies), VV M was involved in the molecular cytogenetic studies, AD K performed, evaluated and interpreted the basic evaluated the GTG-banding, IV S contributed DNA probes for site-specific molecular cytogenetic assay, PV N picked up the case and was involved in the clinical studies and description, YB Y participated in the design of the study and drafted the manuscript, T L evaluated and interpreted the sophisticated molecularcytogenetic studies (MCB-studies) and drafted the manuscript. All authors read and approved the final manuscript.


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Found:Here


So this is what I have found on both Chromosome disorders I hope this helps some one! Thank you for taking the time to read this and try to understand! It is a lot to take in I know!


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2 comments:

shashank said...

Here is a link to more information about the genetics of Chromosome Abnormalities Rings and Markers that was prepared by our genetic counselor and which has links to some useful resources for those dealing with this condition: http://www.accessdna.com/condition/Chromosome_Abnormalities_Rings_and_Markers/239. There is also a phone number listed if you need to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA

Melissa.M.Loss said...

Thank you so Much!!