X and Y Chromosome Related Inheritance Diseases
Chromosomes are structures inside cells that contain a person’s genes. A gene is a segment of deoxyribonucleic acid (DNA) that contains the code to make a specific protein that can play a role in one or more cell types in the body (Genes and Chromosomes for a more detailed overview of genetics). There are many chromosome related inheritance diseases for X and Y.
XY system of sex determination
Sex chromosomes are one of 23 pairs of chromosomes, for:
- XX: female
- XY: male
X linked inheritance
In the case of sex-linked inheritance (hereditary transmission of the X chromosome), only men contract the disease, while women – without being affected or without being massively limited in their visual capacity – could be carriers of the disease. The genetic mutation responsible for this hereditary form is found on the X chromosome.
In practice, we prefer to use the term “linkage to the X chromosome”, because it is the only linkage that has clinical consequences. Most X-linked genetic abnormalities follow a recessive mode of inheritance. They are expressed in all men who carry the gene, but women are only affected if they are homozygous. A man who has only one representative of any X-linked gene is said to be hemizygous. The woman can be homozygous or heterozygous.
It is the woman who has a “sick” gene on one of the two X chromosomes, but hidden by the “healthy” gene on her other (recessive) X chromosome.
The male child of a carrier, who inherited the X chromosome with the mutated gene, will become ill because the Y chromosome inherited from the father is not able to compensate like a healthy gene on the second X chromosome.
The disease gene is located on one of the two X chromosomes of the healthy surrogate mother (XX). Half of male children may be sick, the other half may be healthy. Half of a carrier’s daughters can also be carriers and the other half will not have the disease gene in their genetic makeup.
A father affected with X-chromosomal RP will have daughters that are all carriers, while the sons will all be healthy.
Main Difference – Autosomal vs X-linked
Autosomal and X-linked types are two types of inheritance patterns that describe the inheritance of a particular genetic trait from one generation to another. The main difference between autosomal and X-linked is that Autosomal inheritance is the inheritance of traits determined by autosomal genes whereas X-linked inheritance is the inheritance of traits determined by genes from one of the sex chromosomes. Genes usually come in pairs, each inherited from one parent. Alleles are the variant forms of genes. Dominant alleles prevail over recessive alleles.
- Hair bald
Examples of chromosome chromosome related inheritance diseases linked to X
An anterior chest wall deformity, pectus excavatum in a person with Marfan syndrome. Aurora Bakalli, Tefik Bekteshi, Merita Basha, Afrim Gashi, Afërdita Bakalli and Petrit Ademaj, CC BY-SA 3.0, via Wikimedia Commons
How is a genetic disease linked to the X chromosome transmitted?
Each human cell contains 46 chromosomes, grouped into 23 pairs. The 23rd pair is made up of so-called sex chromosomes (gonosomes): men have one X chromosome and one Y chromosome (XY), women have two X chromosomes (XX). Learn more about genetics…
Diseases whose gene is located on the X chromosome are most often transmitted in a so-called “X-linked recessive” mode. In this case, the disease manifests in male subjects (XY), who have a single mutated copy of the gene, while females (XX) carrying the mutated gene on one of the two X chromosomes are clinically healthy, but carriers of the disease.
Only boys are therefore affected in the maternal line. There is never a father-son transmission.
In humans, the male passes on his Y chromosome to his sons only. This chromosome carries the genes essential for male sex determination. A Y-linked gene has no allele on the X chromosome, such a gene is said to be holandric.
There is no known “disease” transmitted by the Y chromosome, only certain traits such as hypertrichosis of the ears described as being transmitted to boys by their father.
Examples of genetic diseases linked to Y chromosome
Is caused by the presence of an extra copy of the Y chromosome in the cell body (47,XYY). Researchers do not yet know why such a syndrome is manifested by a large size. ncreased risk of learning disabilities and delayed development of speech and language skills. Affected children can have delayed development of motor skills (such as sitting and walking) or weak muscle tone (hypotonia).
Klinefelter syndrome or XXY syndrome
Is caused by the presence of an extra copy of the X chromosome in the cell body (47,XXY). Variants of the syndrome involve more than one supernumerary X. In a small percentage of cases, males with variant Klinefelter syndrome have an extra copy of the X chromosome and the Y chromosome (48,XXYY). The extra chromosomes prevent normal development of sexual functions.
Men suffering from this symptom are rather tall. We also notice at puberty an insufficient development of the testicles; musculature and body hair may also be less prominent.
It affects the function of muscles due to problems with the nerves and muscles in the body, examples:
- Myositis is an inflammation of muscles and their associated tissues, including blood vessels.
- Myasthenia gravis (MG) is an autoimmune neuromuscular disease.
- Amyotrophic lateral sclerosis (ALS) is also called Lou Gehrig’s disease.
Nervous system pathology
Infections, such as meningitis, encephalitis, polio, and epidural abscess. Structural disorders, such as brain or spinal cord injury, Bell’s palsy, cervical spondylosis, carpal tunnel syndrome, brain or spinal cord tumors, peripheral neuropathy, and Guillain-Barré syndrome.
Neuromuscular junction diseases
Dysfunction at location where nerves connect with muscles: Myasthenia gravis – communication problem between nerves and muscles results in muscle weakness and muscle fatigue. Lambert-Eaton Syndrome – often coincides with cancer, causing muscle weakness of the limbs.
Congenital myasthenic syndromes
a diverse group of disorders that have an underlying defect in the transmission of signals from nerve cells to muscles. These disorders are characterized by muscle weakness, which is worsened upon exertion.
X Y linked inheritance
There are many XY linked inheritance diseases, for example:
Down syndrom (or trisomy)
The most common trisomies at birth are trisomies 21, 18 and 13 and mosaic trisomy 8. Trisomies of the sex chromosomes are very frequent and affect both X and Y: 47,XXX, 47,XXY, 47,XYY.
Mosaic Turner Syndrome 45.X/46.XY (also known as X0/XY mosaicism and mixed gonadal dysgenesis or ambiguous genitals)
Is a rare disease of sexual development in humans associated with sex chromosome aneuploidy and Y chromosome mosaicism. This is called a mosaic karyotype because, like tiles in mosaic floors or walls, there is more than one cell type.
Clinical manifestations are highly variable, ranging from partial virilization and ambiguous genitals at birth, to patients with completely male or female gonads. Most people with this karyotype have apparently normal male genitalia and a minority with female genitalia, with a significant number of individuals showing genital abnormalities or intersex characteristics .  Significantly higher than normal numbers of other developmental abnormalities are also found in individuals with X0 / XY mosaicism. Psychomotor development is normal.
Photo credit: XlinkRecessive.jpg: National Institutes of Healthderivative work: Drsrisenthil, Public domain, via Wikimedia Commons
Photo description: the disorder is passed on in an X-linked recessive pattern.