Rareshare would like to acknowledge Dr. Elena Rossi, Associate Professor of Applied Biology and Genetic Medicine, Department of Molecular Medicine, Pavia University, for reviewing this content.

It is extremely rare, with only approximately 190 cases reported in the medical literature so far. 

The cause of the disease is the loss of the genetic information that was contained in the piece of chromosome missing. Each chromosome containes hundreds of genes, depending on the region and size of the deletion, the genes affected will vary between individuals. In general, with a larger portion missing the manifestation of the disease would be more severe.

Chromosomes carry the genetic characteristics of each material and are found in the center (nucleus) of each cell. Humans have 23 pairs of chromosome for a total of 46 chromosomes. These pairs are numbered 1-22, with the 23rd pair being two X chromosomes in women or an X and a Y chromosome in men. Each chromosome also has a long arm called "q" and a short arm called "p." These arms connect at a spot called the centromere.

Most 13q deletions occur spontaneously. They are what is called a de novo change or error and they are not inherited. There is no family history of the disorder and the risk that the parents will have another child with the disorder is minimal. If one parent has what is called a balanced translocation involvng chromosome 13, gametes can have imbalances and the child is at risk of having an unbalanced translocation with both a 13q deletion and an extra region from another chromosome. In this case there is an increased risk of having a second child with a chromosomal abnormality. In few hereditary cases, one parent has a mosaicism with the deletion in only some of the body´s cells.

Children with 13q deletions present different symptoms depending on the region of the chromosome missing. Not all the individuals affected will present all the symptoms described here. The disorder is highly variable in how it affects people.

Infants with chromosome 13q deletion present low weights at birth and low muscle tone (hypotonia). This usually improves after the following months unless there is a feeding problem due to sucking problems or the presence of a cleft palate (a cleft in the roof of the mouth).

Chromosome 13q deletion is also associated with a characteristic facial appearance that includes: small eyes (microphthalmia); wide-set eyes (hypertelorism); high-arched palate; cleft palate; thin forehead; underdeveloped midface (midfacial hypoplasia); small mouth and nose; broad and flat nasal bridge; low set ears; small lower jaw (micrognathia); short neck; low hairline; misaligned and irregular teeth with enamel defects; and a small head circumference (microcephaly). Most children as they age exhibit short stature.

Most of the children with chromosome 13q deletion suffer some kind of learning disability, which can range from mild to moderate to severe. In rare occasions, the piece of chromosome missing is so small that development is not affected.

Children with 13q deletion can also present symptoms in their eyes like coloboma of the iris and choroid (a hole is present in the colored part of the eye, iris, or the vascular layer of the eye, choroid); strabismus; involuntary eye movements (nystagmus); glaucoma; cataracts. These symptoms might cause an impairment of the vision to varying degrees.

In the long arm of chromosome 13 is located a gene named RB1, a tumor suppressor gene that prevents the development of a malignant tumor of the eye known as retinoblastoma. If the region where this gene is located (13q14) is lost, the children are at risk of developing retinoblastoma.

It is common that chromosome 13q deletion affected children present congenital heart defects. Some of these anomalies are holes in the wall (septum) that separates the heart cavities known as the atriums (atrium septum defect) or the ventricles (ventricular septum defect) or the narrowing of the valves that connect the heart with the blood vessels (pulmonary stenosis in the case of the pulmonary valve or coarction of the aorta in the case of the aorta valve).

Brain abnormalities are also found in affected individuals. These may include: epilepsy; the early closure of the skull bones (craniosynostosis); paralysis of the leg and foot (spastic displegia); underdeveloped brain (cerebral hypotorphy); underdevelopment or absence of the nerves that connect the two sides of the brain (agenesis of the corpus callosum); underdeveloped cerebellum (cerebellar hypoplasia); Dandy-Walker syndrome (a brain abnormality that involves the cerebellum); deafness if the hearing nerves are affected; holoprosencephaly (the brain develops as only one lobe and does not divide into two hemispheres); and spina bifida.

The skeleton might also be affected. Some of the conditions described are: dislocation of the hip joint; clubfoot; vertebral abnormalities; webbed toes (syndactyly); and finger abnormalities.

Other organ systems commonly affected are the endocrine system, the digestive system and the genitourinary system. Some of the symptoms in this category are underdevelopment of the kidneys, thymus, thyroid, pancreas, adrenal glands or genitalia; retention testis (the testes do not descend into the scrotum); malpositioning of the anus; gastric reflux; Hirschsprung´s disease (the nerves that control the intestine movement are absent what leads to constipation).

Chromosome 13q deletion can be diagnosed by conventional cytogenetics, in which the chromosomes are studied under the microscope, or by array comparative genomic hybridisation (array-CGH), which allows the detection and a detail molecular characterization of small deletions/dyplications not visible with a classical karyopyte. Chromosome 13q deletion can be diagnosed prenatally.

Karyotype is basically taking a picture of a person’s chromosome makeup. It allows a physician to analyze the number and the structure of the chromosomes and to identify gross structural changes and numerical abnormalities. Array-competitive genomic hybridization, also called molecular karyotyping, is a technique which instead of using metaphase chromosomes, uses patient´s DNA. This DNA and a DNA from a healthy control are labeled with different fluorochromes and hybridized to a slide, an array, containing small segments of DNA, representative of the whole genome, as the targets for analysis. After hybridization, a scanner measures the fluorescent signals and a computer software analyzes the data and generates a plot for each chromosome where gains and losses of specific chromosomal regions are visible.

Unfortunately, there is no cure for chromosome 13q deletion and the treatment is based on the management of the symptoms that each patient presents. Children should be thoroughy examined after a diagnosis to determine what are the particular disease manifestations and to determine what are the best treatment options. Effective treatment requires the involvement of different specialists that may include a neurologist, a physical therapist, an occupational therapist, a psychologist, a special education teacher, etc.

Plastic surgery can aid in the case of cleft palate, but several interventions over a number of years are needed. Surgery is also required in the case of certain congenital heart defects such as atrium or ventricular septum defect.

A dentist can recommend an orthodontic treatment in case of teeth misalignment or irregularities. The defects in the enamel can also be treated protecting the teeth with an special coating.

Hip luxation and clubfoot can be treated with splints or a plaster cast. In some occassions, surgery could be required. In case of other skeletal manifestations, if they do not interfere with the daily living, surgery is not considered necessary.

Abnormalities in the kidney or the gastrointestinal tract can be considered for surgery intervention. The gastric reflux is treated with medicines. If the testes have not descended, it can be treated with hormones and/or surgery.

Periodic examinations by an ophthalmologist should be performed due to the risk of retinoblastoma. Glaucoma can be treated by eye drops. Surgery might be performed in the case of cataracts.

Treatment is required throughout a patient´s life, and adults with chromosome 13q deletion often require some sort of assistance to cope with daily activities (adult day care, adapted housing,…). Prognosis is diffetent in different cases and depends on the severity of the signs and symptoms and associated complications, if any. Individuals with chromosome 13q deletion can have a reduced lifespan.

Chromosome 13q deletion. Genetic and Rare Diseases Information Center (GARD) website. https://rarediseases.info.nih.gov/diseases/1738/chromosome-13q-deletion

13q deletions various. Unique. https://www.rarechromo.org/information/Chromosome%2013/13q%20deletions%20various%20FTNW.pdf

13q deletion syndrome. Socialstylrelsen website. http://www.socialstyrelsen.se/rarediseases/13qdeletionsyndrome

Wang, Y. P., et al. (2017). "Chromosome 13q deletion syndrome involving 13q31qter: A case report." Mol Med Rep 15(6): 3658-3664.