Thanatophoric dysplasia

Thanatophoric Dysplasia(TD)

: is the most common form of skeletal dysplasia( severe skeletal disorder) , lethal in the neonatal period .

Characterized by:  extremely short limbs, folds of extra skin on the arms and legs, a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes.

Type I thanatophoric dysplasia: presence of curved thigh bones and flattened bones of the spine (platyspondyly). 

Type II thanatophoric dysplasia:  straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.

cause: 

Mutations in the FGFR3 gene (the short-arm of chromosome 4)

 FGFR3 gene: encoded Fibroblast growth factor receptor 3 protein in human. It is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly active, which leads to the severe disturbances in bone growth that are characteristic of thanatophoric dysplasia.

FGFR3 protein is part of the tyrosine kinase receptor family. FGFR3 is a negative regulator of bone growth.

Thanatophoric dysplasia initiate by sending negative signals to the cartilage cells .These signals occur when ligand binding within the chondrocytes induces receptor homodimerization and heterodimerization. As aresult, activation of tyrosine kinase function potentiates many effects on cell growth and differentiation.

http://emedicine.medscape.com/article/949591-overview#a0104

http://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia

Swyer syndrome

Swyer syndrome

: A person is born without functional gonads and known as XY gonadal dysgenesis.

:is a condition in which individuals with one X chromosome and one Y chromosome in each cell, the pattern normally found in males, have a female appearance. 

People with this disorder have female external genitalia and a normal uterus and Fallopian tubes. However, they do not have functional gonads (ovaries or testes). 

Their gonads are minimally developed clumps of tissue present instead testes or ovaries.

This kind of gonad in swyer syndrome are known as gonadal streaks. These abnormal gonads often become cancerous, so they are usually removed surgically early in life.

Causes:

1)    Mutations in the SRY gene (15 % to 20 %): prevent production of the sex-determining region Y protein or result in the production of a nonfunctioning protein. This fetus will develop as a female despite having a Y chromosome.

2)     Mutations in the NR5A1 and DHH genes (small number): The NR5A1 gene produce transcription factor steroidogenic factor 1 that help to produce sex hormones and development of male sexual characteristics. The DHH gene produce a member of the hedgehog protein family. Hedgehog proteins are important for early development in many parts of the body. Mutations in the NR5A1 and DHH genes impair the process of male sexual differentiation, causing to develop a female appearance despite having a Y chromosome.

3)     Changing in the NR0B1 gene (small number): The NR0B1 gene provides a DAX1 protein that have important role in the development and function of gonads. A duplication of a region in the X chromosome can result in an extra copy of the NR0B1 gene, which leads to the production of extra DAX1 protein. Before birth, an excess of DAX1 protein prevents the formation of male reproductive tissues, including the testes and male external genitalia.

These people are typically raised as females and have a female gender identity.

Treatment: hormone replacement therapy during adolescence to induce menstruation and development of female secondary sex characteristics such as breast enlargement and body hair.

http://www.webmd.com/a-to-z-guides/swyer-syndrome

http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1204/viewAbstract

Leydig cell hypoplasia

Leydig cell hypoplasia

: a rare autosomal  recessive genetic and endocrine syndrome that affects male sexual development. 

characterized by: underdevelopment (hypoplasia) of Leydig cells in the testes.

Leydig cells function: secrete androgen that are important for normal male sexual development before birth and during puberty.

Affected person:  typical male chromosomal pattern (46,XY), 

have a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), and a scrotum divided into two lobes (bifid scrotum), ambiguous genitalia.

They do not develop secondary sex characteristics, such as increased body hair, at puberty.

Mutations in the LHCGR gene cause Leydig cell hypoplasia.

 The LHCGR gene provides the luteinizing hormone/chorionic gonadotropin receptor.

 In males: chorionic gonadotropin stimulates the development of Leydig cells in the testes and LH cause produce androgens like testosterone  that control male sexual development and reproduction. 

In females: LH triggers the release of egg cells from the ovary (ovulation). Chorionic gonadotropin is produced during pregnancy and helps maintain conditions necessary for the pregnancy to continue.

Leydig cell hypoplasia:  disrupt LH/chorionic gonadotropin receptor function.

In males:  poorly developed or absent Leydig cells and impaired production of testosterone. 

A lack of testosterone: poorly development of male sexual organs before birth.

http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410X.1998.00503.x/pdf

http://press.endocrine.org/doi/pdf/10.1210/jc.2004-0298

http://link.springer.com/chapter/10.1007/978-1-4419-8002-1_32

DOWN SYNDROME

DOWN SYNDROME

:is a chromosomal condition caused when abnormal cell division results in extra genetic material from chromosome 21.

 

causes intellectual disability (developmental delays), Flattened facial features, Protruding tongue, small stature, an upward slant to the eyes, single deep crease across the center of the palm and weak muscle tone in infancy.

One in every 691 babies in the United States is born with Down syndrome. Approximately 400,000 Americans have Down syndrome and about 6,000 babies with Down syndrome are born in the United States each year.

There are three types of Down syndrome:  trisomy 21 (nondisjunction), translocation and mosaicism.                             

About 95% of cases Down syndrome are usually caused by nondisjunction that is called trisomy 21.   Nondisjunction results in abnormal cell division during the development of the sperm cell or the egg cell with three copies of chromosome 21 instead of the usual two. 

Mosaicism occurs when nondisjunction of chromosome 21 takes place in one but not all cells. It is caused by abnormal cell division after fertilization. Children have some cells with an extra copy of chromosome 21.  Mosaicism is rare and accounts for about 1% of all cases of Down syndrome.

About 4% of all cases of Down syndrome are translocation.  In translocation, part of chromosome 21 becomes attaches to another chromosome, typically chromosome 14.  These children have the usual two copies of chromosome 21 and total number of chromosomes in the cells remains 46 but an extra part of chromosome 21 causes the characteristics of Down syndrome. 

Risk factors: advancing maternal age, having had one child with Down syndrome, and being carriers of the genetic translocation for Down syndrome.

I have one cousin that has Down Syndrome because of  his mother maternal age. I think that this kind of children needs really good educational support. My cousin knew the capital city of most of the countries in the world at age 4. His mom and sister really support him and speak with him all the time. it is really good for them to have as much as communication with people. they can not grow up like other children but at least they can be good in their ways. 

http://geneticdisordersp7.wikispaces.com/Down+Syndrome

http://comd281-summerwiki.wikispaces.com/Group+5++Down+Syndrome

http://www.chw.org/medical-care/genetics-and-genomics-program/medical-genetics/chromosome-abnormalities/types-of-chromosome-abnormalities/structural-abnormalities/translocations/

http://ghr.nlm.nih.gov/condition/down-syndrome

PENTA X SYNDROME

PENTA X SYNDROME

• 49, XXXXX Chromosome Constitution
• 49, XXXXX Karyotype
• 49,XXXXX Syndrome
• Pentasomy X
• XXXXX Syndrome

penta X Syndrome is a rare chromosomal disorder that affects females.

In Penta X Syndrome, there are three additional (or a total of five) X chromosomes in the nuclei of body cells (pentasomy X).

The condition is typically characterized by:

 Moderate to severe mental retardation, short stature, malformations of the skull and facial region, and other physical abnormalities.Characteristic craniofacial malformations may include upslanting eyelid folds, a flat nasal bridge, malformed ears, a short neck with a low hairline.

Penta X Syndrome is characteristically associated with growth delays before birth.

Females with Penta X Syndrome have 49 chromosomes, five of which are X chromosomes. The presence of the three additional X chromosomes results from errors during the division of reproductive cells in one of the parents (nondisjunction during meiosis).

 Evidence suggests that the extra X chromosomes are typically derived from the mother.

 Researchers indicate that the risk of such errors may increase with advanced parental age.

http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/790/viewFullReport

http://mdiascurra.tumblr.com/

Cadherin

: Calcium (Ca2+) -dependent adhesion, class of type -1 transmembrane proteins.

Important roles: cell adhesion, forming adherens junctions to bind cells within tissues together.

The cadherin superfamily:  cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo)

 Each cadherin has a small cytoplasmic component, a transmembrane component, and the remaining bulk of the protein is extra-cellular (outside the cell).

Tissue morphogenesis during development is dependent on activities of the cadherin family of cell–cell adhesion proteins.

The extracellular domain of cadherins contains characteristic repeats that regulate homophilic and heterophilic interactions during adhesion and cell sorting.

Although cadherins may have originated to facilitate mechanical cell–cell adhesion, they have evolved to function in many other aspects of morphogenesis. Cadherin also interactions with a wide range of binding partners that modify their expression and adhesion activity by local regulation of the actin cytoskeleton and diverse signaling pathways.

http://www.fastbleep.com/biology-notes/31/178/1022
Halbleib J. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis.Genes & Dev. 2006. 20: 3199-3214.      

Fibroblast growth factor (FGFs)

: A family of growth factor.

Involved in: angiogenesis, wound healing, embryonic development and various endocrine signaling pathways

The FGFs: heparin-binding proteins and interactions with cell-surface-associated heparin sulfate proteoglycans: be essential for FGF signal transduction.

Important role:  involved in the regulation of many developmental processes including patterning, morphogenesis, differentiation, cell proliferation or migration.

The FGFs: are secreted molecules which function through the activation of specific tyrosine kinases receptors, the FGF receptors that transduce the signal by activating different pathways including the Ras/MAP kinase and the phospholipase-C gamma pathways.

 FGFs are such a diverse set of activities requires a tight control of the transduction signal which is achieved through the induction of different feedback inhibitors such as the Sproutys, Sef and MAP kinase phosphatase 3 which are responsible for the attenuation of FGF signals, limiting FGF activities in time and space.

                             

http://www.nature.com/nrn/journal/v8/n8/full/nrn2189.html
Thisse B,Thisse Ch.Functions and regulations of fibroblast growth factor signaling during embryonic development   .Developmental Biology, Volume 295, Issue 1, 1 July 2006, Page 294.

Wnt signaling pathway

: are a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell.

Three Wnt signaling pathways: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway.

The embryonic processes include:  body axis patterning, cell fate specification, cell proliferation, and cell migration.  These processes are necessary for proper formation of important tissues including bone, heart, and muscle.

 Its role in embryonic development was discovered when genetic mutations in proteins in the Wnt pathway produced abnormal fruit fly embryos. Later research found that the genes responsible for these abnormalities also influenced breast cancer development in mice.

http://molehr.oxfordjournals.org/content/15/4/215/F1.expansion.
Tata Purushothama Rao,Michael KühlAn. Updated Overview on Wnt Signaling Pathways.
 .Circulation Research. 2010;106:12 1798-1806.