Chromosome defects

Main symptoms: short stature due to SHOX-gene deletion (preventable with growth hormone treatment), webbed neck due to dilated lymphatic channels (called cystic hygroma), shield chest with widely spaced nipples, ovarian dysgenesis ("streak ovaries"), congenital heart disease (20-50%; bicuspid aortic valve, coarctation, hypoplastic left heart), horseshoe kidney, hypothyroidism (10-30%) and early osteoporosis. Most have an IQ that falls within normal limits.
Fertility: ovaries are replaced by fibrous stroma, which leads to decreased production of estradiol and progesterone which in turn leads to increased production of LH and FSH from the pituitary gland. This leads to primary amenorrhea with delayed puberty. Most often no oocytes are present after the age of 2, in about 5-10% of cases, enough ovarian development has occured to allow for fertility.
15% of spontanious abortions are considered to be caused by Turner syndrome.
80% of cases are due to paternal nondisjunction (most are nonviable).
75% of cases have mosaicism as most non-mosaicsm cases are non-viable.
Can also be caused by chromosomal structural abnormalities (for example deletion of part of chromosome X or isochromosomes).

• Statistics: 1:3.000 live births
• Treatment: hormonal treatment for growth and puberty. Surgical treatment if needed.

Main symptoms: Testicular atrophy, small penis and gynecomastia due to decreased testosterone and increased estrogen production. They tend to be very tall and have long extremities and broad hips. Mitral valve prolapse is present in 50% of individuals. Most individuals have an IQ within the normal limits, however many experience trouble with learning language-based skills. These individuals are often described as shy and reserved, and have an increased risk for developing anxiety and depression.
Hypogonadism pathology:Over time in the testicles of men with kleinfelter syndrome, seminiferous tubules suffer fibrosis causing a blokage of the tubules. The blokage leads to azoospermia upon ejactulation and a loss of Sertoli cells. This leads to inhibin B reduction which leads to increased FSH production. FSH asserts its affect on the Leydig cells which leads to increased production of aromatase which converts testosterone into estradiol. It is though believed that the main reason for hypogonadism and feminine symptoms, is not this increase in aromatase, but due to dysfunctional interaction between testosterone and androgen receptors. These testicular changes appear in puberty and cause hypogonadism (testicular atrophy), gynecomastia and diminished facial, body and pubic hair. Micropenis is caused by lack of testosterone in utero.
Fertility: It was previously thought that all Klinefelter men were infertile, it has been recently shown that about 50% of these men have sperm that can be detected and retrieved by testicular sperm extraction (TESE). The likelihood of finding sperm is higher the younger the individual is and one study has even shown that sperm can be found in 70% of ejculated semen of Klinefelter individuals in the age of 12 to 20. It is therefore recommended to advise fertility preservation as soon as possible.

90% of cases are due to nondisjuction, the rest is caused by mosaicism (most common 46,XY + 47,XXY).

• Statistics: 1:500-1.000 live births
• Treatment: Neurophysical assesment can be useful. Testosterone supplement treatment may prevent the development of some of the symptoms associated with high estrogen, the age at which the treatment should start and is individualised.

These individuals are rarely diagnosed, as symptoms tend to be mild. Physical symptoms that can be present are hypotonia, increased height (longer legs), mild learning disabilities, especially concerning speech and language development. In some cases mild facial features can be seen as hypertelorism, epicanthic folds and upslanting palpebral fissures. Clinodactyly and hyperextendible joints can be seen. IQ is on average 85-90 and most live normal lives. Average age for menopause is 45 years, 5 years earlier than expected, for most fertility is normal.

• Statistics: 1:1.000 live births
• Symptoms: Mild if present at all
• Treatment: neurodevelopmental evaluation could be helpful to see if the child needs additional assistance.

These individuals are normally undiagnosed, as few show obvious symptoms. The most common symptom is tall stature, severe acne and a mild learning disability, especially speech and language development. IQ is normal, though often 10-15 points lower than the IQ of siblings. In some cases, behavioral problems like hyperactivity, increased impulsivity or anti-social symptoms can be present. Fertility and sexual development seems to remain normal.

• Statistics: 1:1.000 live births
• Symptoms: usually none.
• Treatment: speech therapy can be useful for some.

Multiple malformations: midline facial defects (cleft lip and palate, holoproscencephaly, microopthalmia some with cyclopia), meningomyelocele, omphalocele, polydactyly, rocker-bottom feet, abnormal genitalia, heart defects and more.
Most children (90%) will die within the first year after birth, where median survival i 7-10 days.

• Statistics: 1:5.000-15.000 (geographical variation)
• Treatment: Supportive. Surgery to correct birth defects.

Multiple malformation (>100 symptoms described): microcephaly with a prominent occiput, holoprosencephaly, cleft lip and palate with a small jaw, low-set and malformed ears, growth retardation, arthrogryposis, clenched hands and hypoplastic nails, rocker-bottom feet, omphalocele, heart defects, malformation of lungs, trachea and esophagus, malformation of genitals and kidneys.
90-95% of fetuses do not live until birth and die in utero, those who live are more likely to be female. 90% of those who survive, die within the first year after birth due to organ malformations. Those who survive longer than 1 year often have moscaism of trisomy 18, meaning that the error happened after the formation of the fetus and not all of the cells have trisomy 18.

• Statistics: 1:8.000
• Treatment: Supportive. Surgery to correct birth defects.

Multiple malformations: flattened face and nasal bridge, almond shaped eyes with upslanting palpebral fissures and epicanthal folds, small folded low-set ears. Brushfield spots. Short neck. Intellectual disability (average IQ is 50-60). Seizures are common. Hypotonia. Heart defects (most common (40%) is atrioventricular septal defect and second most common (32%) is ventricular septal defect), malformation of the GI-tract (duodenal atresia, Hirschsprung disease). Hearing loss, both conductive and sensory, is common due to anatomical malformation of the ear structures. Delayed puberty is expected. Transient neutrophilia, polycythemia and thrombocytopenia can be observed in the first weeks of life. These individuals are at increased risk for developing AML and ALL, and over 50% will have developed Alzheimer's before 60 years of age. Atlantoaxial instability can be present, which can lead to spinal cord compression. It is therefore vital to screen for this instability before anesthesia.
Most fetuses (50-75%) do not survive until birth.
5% of trisomy 21 are due to Robertsonian translocation found in either parent or due to mosaicism.

• Statistics: 1:700
• Treatment: Surgical and supportive.