1p36 Deletion Syndrome

• 1p36 deletion syndrome is a genetic disorder: 1 is the chromosome number that has deleted DNA, p is the short arm of the chromosome (shortest length of DNA above the centromere) that contains designated area 36 that is missing DNA.
• DNA missing from area 1p36 is responsible for the broad range of symptoms such as changes in facial structures, severe learning disabilities, severe oral communication problems, as well as heart, muscle, breathing, eye, and other problems.
• Not all individuals affected by 1p36 syndrome develop all problems. The severity is likely related to which areas and how much DNA is missing in 1p36.
• Treatment for 1p36 deletion syndrome is mainly aimed at reducing the severity of symptoms with consultations with experts in the medical, surgical, and behavioral fields.
• Each person with 1p36 deletion syndrome is an individual with problems specifically related to their 1p36 DNA loss. With appropriate consultation and effort on both the affected individual and their family or caregiver, a chance to develop rewarding relationships should be available for many people.
• The genetic problem is so new that life expectancy and overall prognosis are not yet well defined. There are reports that some individuals with 1p36 deletion syndrome live to adulthood.
• This condition is sometimes referred to as 1p36 syndrome or 1p36 deletion, and ongoing research may provide more insight into its long-term impact.

As humans, we all normally share 23 chromosomes from each parent, for a total of 46. But what happens when some of the genetic material (genes made from DNA) in the chromosomes is missing? The outcome depends on the functions that the genetic material controls. Unfortunately, in a relatively newly identified problem, 1p36 deletion syndrome (first deletion noted in 1981 and in 1997, the clinical features first outlined), a small segment of missing DNA results in large problems for individuals missing the DNA and for their families.

The name of the problem is 1p36 deletion syndrome. This numeric name means that it affects chromosome #1, the largest human chromosome. It precisely affects the area on the #1 chromosome that is on a short arm of the chromosome (p means the short arm above the centromere that joins the two parental copies of chromosome 1, and area 36 is where the missing DNA should be located). In recent years (about 2005-08), recent diagnostic tests known as fluorescent in situ hybridization (FISH) and microarray comparative genomic hybridization (array CGH) have been developed to definitively diagnose the 1p36 deletion syndrome. CGH may determine how much DNA is missing in individuals affected by 1p36 deletion syndrome.

1p36 deletion syndrome is often associated with various developmental delays, intellectual disabilities, and other health issues. The specific symptoms of 1p36 deletion syndrome can vary widely, even among individuals with the same genetic deletion. However, many affected individuals experience challenges with motor skills, speech, and cognitive development due to the missing genetic material. Health care providers need to be aware of the signs and symptoms of 1p36 deletion syndrome to offer early interventions and support for affected individuals and their families.

Missing DNA in this section is very influential on a person's overall development and is often unnoticed until the newborn or infant is noted to miss physical or developmental landmarks. These missed or severely delayed landmarks comprise the symptoms and signs of 1p36 deletion syndrome. Not all symptoms will be present in each individual because there is variation from person to person and, in general, most researchers think that the more DNA missing from 1p36, the more intense or apparent these symptoms will appear.

Many individuals with 1p36 deletion syndrome will have a small head size that is short and wide; many have noticeable facial features of deep-set eyes with straight-appearing eyebrows, a sunken-appearing face with a broad flat nose and an elongated area from nose to mouth, a pointed chin, and low-set ears that are rotated backwards and are abnormally shaped. Some individuals are preliminarily diagnosed from their appearance described above. Others may have less noticeable physical symptoms and require FISH or CGH tests for diagnosis to confirm 1p36 deletion syndrome.

To confirm or establish the diagnosis, it is appropriate to test any individual suspected of having 1p36 deletion syndrome as follows:

• Conventional cytogenetic studies to detect large deletions (i.e., greater than 5 Mb) and more complex cytogenetic rearrangements (unbalanced chromosome translocations)
• FISH with at least two subtelomeric region-specific probes (Vysis 1p subtel probe, Vysis p58 probe; D1Z2 Oncor probe or CEB108/T7) to detect unbalanced translocations and to identify parental chromosome rearrangements
• Deletion/duplication analysis by CMA to detect smaller deletions (i.e., 5 Mb or less) or interstitial deletions or complex rearrangements

There are other problems (symptoms) that many individuals with 1p36 deletion syndrome develop:

• About 90% have severe learning disabilities.
• About 75% will have no ability to form words, the other approximately 25% will only develop a few words or phrases.
• About 70% develop types of heart problems.
• About 50% will develop seizures, behavior problems, and hearing problems.
• Other problems such as weak muscle tone, breathing problems, eye problems, swallowing problems, genital malformations (usually minor in males), and metabolic problems have been reported in individuals with 1p36 deletion syndrome.

Treatment for 1p36 deletion syndrome is limited; symptomatic treatment is the usual treatment available. The heart, eye, muscle tone, and swallowing problems may be reduced by specialists in those fields. The earlier the diagnosis and treatment, the more likely these problems will become manageable or minimized. Some clinicians report good results with behavior modification training. Some individuals affected with 1p36 deletion syndrome do well and can participate in many social events, but not all individuals are successful.

Compassion, patience, and understanding of the extent of an individual's capabilities can allow an individual with 1p36 deletion syndrome to have a loving and rewarding relationship with family and friends. Some affected individuals may be able to learn to communicate with body and sign language; this ability may take considerable effort and training on both the affected person and caregiver's part to develop.

Part of the prognosis for individuals with 1p36 deletion syndrome really depends on how much of DNA is missing from the p36 region. Some researchers now list p36 as p36.1 to p36.3, with p36.3 as the most amount of DNA missing and having the worst prognosis (poor, with severe symptoms). However, even these individuals may have some responses to the treatment listed above. Consequently, some individuals may have a relatively good prognosis (a loving relationship with understanding and patient caregivers and family members) to a poor prognosis and early death from significant physical problems. While 1p36 deletion syndrome is so new that data on projected lifespan is lacking, there are reports in the medical literature that some patients reach adulthood. How many of those that have the 1p36 deletion syndrome now and live on will help determine the life expectancy for future patients with 1p36 deficiency syndrome.

Current research is focusing on collecting blood from families with a child who has been diagnosed with a chromosomal disorder, including microdeletions, in order to further develop a non-invasive prenatal screening test based on fetal DNA isolated from maternal blood.

This research could potentially aid in the early detection of 1p36 deletion syndrome. Understanding the genetic makeup of families affected by 1p36 deletion syndrome is crucial for the development of more effective diagnostic tools and treatments. Researchers are also investigating how 1p36 deletion syndrome may be linked to other genetic disorders and exploring potential therapies to manage or alleviate some of its associated symptoms.

• Is there a cure for 1p36? Currently, there is no cure for 1p36 deletion syndrome, a rare genetic disorder caused by the partial loss of chromosome 1. Treatment mainly focuses on managing the symptoms, including intellectual disability, seizures, heart defects, and other physical and developmental challenges, through various medical and therapeutic interventions. Research into gene therapy and other treatments is ongoing, but no definitive cure has been found.
• Is 1p36 deletion syndrome rare? 1p36 deletion syndrome is considered a rare genetic disorder, affecting approximately 1 in 5,000 to 1 in 10,000 live births. It is caused by the deletion of genetic material on the short arm of chromosome 1, leading to developmental, intellectual, and physical challenges. Due to its rarity, affected individuals often require specialized care and management.
• Can 1p36 deletion syndrome be detected before birth? 1p36 deletion syndrome can be detected before birth through prenatal genetic testing, such as amniocentesis or chorionic villus sampling (CVS), which can analyze the fetus's chromosomes. While non-invasive prenatal screening and advanced imaging techniques may offer early clues, a definitive diagnosis typically requires chromosomal analysis. Early detection enables better preparation for managing the condition after birth.
• What are the side effects of 1p36 deletion syndrome? 1p36 deletion syndrome can cause a range of side effects, including developmental delays, intellectual disabilities, seizures, and speech and motor impairments. Affected individuals may also experience heart defects, vision problems, and hearing loss. Other common features include a small head size (microcephaly), low muscle tone, speech delays, and behavioral challenges.
• What are the facial features of 1p36 deletion syndrome? Facial features commonly associated with 1p36 deletion syndrome include a small, rounded head, a prominent forehead, and a flat or broad nasal bridge. Affected individuals may also have a thin upper lip, downturned corners of the mouth, a prominent chin, and widely spaced eyes. These features, along with other developmental characteristics, can vary in severity among affected individuals.