There are two groups of people with 18q deletions: those with deletions involving the end of the chromosome (known as distal deletions), and those with deletions closer to the centromere (known as proximal deletions). The goal of this article is to describe the major features of proximal deletions of 18q, which we will refer to as “proximal 18q-” for the rest of this article . This information contained here was obtained from a thorough review of the literature as well as from the experiences of the Chromosome 18 Clinical Research Center. This information may help you and your healthcare team make decisions about how to care for a person with proximal 18q-.
As you read through this article, remember that no two people with proximal 18q- are exactly alike. One person may have different medical and developmental concerns from another person with proximal 18q-. Also, remember that no one with proximal 18q- will have all of the features listed below. In addition, people with proximal 18q- share many features with their family members. They will also have their own unique skills and abilities which you will not find in the following list.
Research is critical. As we learn more about proximal 18q-, we will also learn more about how to best treat it. This will improve the health and development of people with proximal 18q-.
Background
Proximal 18q- was first described in 1974. Since then, about two dozen cases have been reported in the literature. This condition may also be called “interstitial 18q-”. Because this condition is even less common than distal 18q-, the information presented here is based on fewer case reports.
Genetic Basis of Proximal 18q-
Although distal 18q- and proximal 18q- are both caused by deletions on the long arm of chromosome 18, the location of the deletions on the long arm are different.
In order to understand the difference between distal and proximal 18q-, it is important to know about the structure of chromosome 18. Every chromosome, including chromosome 18, has a characteristic black and white banding pattern and a constriction (called a centromere) in a characteristic location somewhere along its length. These two things, the banding pattern and the centromere, make each chromosome recognizable to a trained eye.
As you can see, the centromere of each chromosome is not exactly in the middle of the chromosome. This makes the chromosome appear as if it had two distinct segments of unequal length. These segments are called arms. The shorter arm (called "p" for petit) is always shown on top. The longer arm is called the “q” arm and is shown below the p arm.
The bands on each chromosome arm divide it up into regions. The regions are numbered starting at the centromere and progressing to the end of the chromosome arm. Below is a diagram that shows how the bands of chromosome 18 are labeled.
Idiogram Album: Human copyright 1991 David Adler and Michael Willis
Proximal deletions involve bands between the centromere and band 21.1. Proximal deletions usually extend from band 12.1 or 12.2 to 21.1. There have also been some individuals with a deletion that starts at band 11.2 and extends to 21.1. These deletions are usually “interstitial” deletions. This means that the deletion does not include the tip of the chromosome. In contrast, most distal deletions start at band 21, 22, or 23. These delections usually include the tip of the chromosome. The diagram below shows which parts of chromosome 18 are involved with these two different types of deletions.
Characteristics of Proximal 18q-
Development
Proximal 18q- changes the way the brain develops and works.
Infants, toddlers and young children with proximal 18q- may develop more slowly than those without proximal 18q-. For example, it may take a little longer for them to roll over, sit, crawl, and walk. It may also take longer for them to reach for and grab toys, hold a bottle, and to feed themselves. Language skills may also develop later than their peers.
Children and adults with proximal 18q- may have some mental impairment, though the degree of impairment varies between individuals. It does appear that many individuals with proximal 18q- have more difficulties with expressive speech than with receptive speech. That is, they may be better at understanding others than at expressing themselves through speech.
Neurologic Changes
People with proximal 18q- frequently have low muscle tone (hypotonia). About half of people with proximal 18q- have seizures.
If a person has neurological problems, they may see a neurologist. If seizures are suspected, a doctor may request an electroencephalogram (EEG).
MRI Changes
Some people with proximal 18q- have changes in the structure of their brain that can only be detected with an MRI. For example, two people have been identified with a thin corpus callosum. The corpus callosum is the bundle of nerves that connect the right and the left sides of the brain. Other people have been diagnosed with “enlarged lateral ventricles”. This simply means that the spaces that contain the cerebrospinal fluid in the brain are larger than expected. Lastly, several individuals evaluated at the Chromosome 18 Clinical Research Center had “Virchow-Robin perivascular spaces”. Basically, this means that some extra space was noted surrounding some of the blood vessels in the brain.
Eyes and Vision
Vision problems are fairly common. The eyes may be crossed (strabismus). Some people with 18q- may have problems focusing their eyes (refractive errors). Refractive errors include near-sightedness, far-sightedness, and astigmatism.
Because vision problems are possible, people with proximal 18q- should have regular eye exams.
Ear Infections and Hearing Loss
Babies, toddlers, and children with proximal 18q- may have more ear infections than other children. In turn, this may lead to hearing problems. Therefore, it is important to identify and treat ear infections. Most of the time, medicine is prescribed to treat the ear infection. Some children may require surgery to insert tubes in the ears to reduce the number of ear infections.
Hearing problems are not very common in people with proximal 18q-. There have only been two people with proximal 18q- and hearing loss. Both of them had hearing loss caused by recurrent ear infections and the placement of ear tubes.
Heart
Heart defects are rare in babies with proximal 18q-. There has been one individual reported with a patent foramen ovale, or a small hole in the wall separating two chambers of the heart.
In order to be sure that a person with proximal 18q- does not have a heart defect, a physician may order an ultrasound of the heart (echocardiogram) to look for defects.
Musculoskeletal Changes
People with proximal 18q- may have foot abnormalities. A couple of individuals have been diagnosed with clubfoot (talipes equinovarus). Several others have developed flat feet(pes planus). Some may also develop a curvature of the spine (scoliosis). All of these bone problems can affect the way that they walk and may lead to gait abnormalities.
People with foot, knee, or spinal changes may see an orthopedic specialist. Braces and inserts, surgery, and therapy may help in addressing orthopedic concerns.
Genitourinary
Although it is uncommon, boys with proximal 18q- may have some changes in the urogenital system. Two boys reported in the literature had testicles that were not fully descended (cryptorchidism). Another baby with proximal 18q- had a birth defect of the bladder that required surgical correction.
Still, the majority of babies with proximal 18q- do not have any problems in the genitourinary tract.
Growth
Children and adults may have changes in their growth patterns. Children with proximal 18q- are often small for their age. Unlike individuals with distal 18q-, however, no one with proximal 18q- has been diagnosed with growth hormone deficiency.
Adults with Proximal 18q-
There have been a handful of adults with proximal 18q- reported in the scientific literature. Most of these adults are in the same family and have a larger deletion than others with proximal 18q-. Their deletion started at band 11.2. Two of these adults have passed away from cancer. One passed away from lymphoma and the other from a particular form of brain tumor (glioblastoma).
Both of these individuals as well as one more adult in the family had an autopsy after they passed away. These autopsies showed some changes in the brain. These changes are neurodegenerative, meaning that they involved the degradation of some of the brain cells. Unfortunately, we do not know whether or how this relates to the 18q deletion.
Lastly, several adults from different families have been diagnosed with cataracts. Thus, it is important for adults to have routine ophthalmologic evaluations.
Facial Features
People with proximal 18q- may have facial features that are slightly different from other family members. These changes do not affect a child’s health or development. They are simply small differences that might be noted by a doctor.
They may have a prominent forehead, and the middle of their face may look flat. Their eyes may be deep-set. Although people with proximal 18q- may have facial features in common with one another, it is important to remember that they also have features in common with their family members.
Family Planning and Genetic Counseling
Many parents wonder, “If we have another child, what is the chance that our next child will have proximal 18q-?”
The answer to this question depends on whether a chromosome change has been identified in one of the parents. In most cases, neither parent has a chromosome change. In this situation, the chance that a couple will have another child with 18q- is low.
In a small number of families, one parent has an 18q deletion. If a parent has a deletion, there is a 50% chance that they will have a child with 18q-.
In some families, the deletion of 18q results from a more complicated chromosome rearrangement in a parent, such as an insertion. In this situation, the likelihood that another child would have a chromosome change depends on what type of rearrangement the parent has and which chromosomes are involved.
If you have questions about the implications of a chromosome change for other family members, we recommend contacting a genetics provider.
For Additional Information
The information provided here is general information based on the literature as well as the experiences in the Chromosome 18 Clinical Research Center. However, every person with 18q- is different. Therefore, this information should not replace professional medical advice, diagnosis, or treatment. If you have questions or concerns, you may find it helpful to talk with a clinical geneticist or genetic counselor. You can locate a genetics provider at one of these sites:
GeneTests Clinic Directory
National Society of Genetic Counselors
Selected References:
Chudley AE, Bauder F, Ray M, McAlpine PJ, Pena SDJ, Hamerton JL (1974). Familial mental retardation in a family with an inherited chromosome rearrangement. J Med Genet 11: 353-366.
Chudley AE, Kovnats S, Ray M (1992). recognizable behavioral and somatic phenotype in patients with proximal interstitial 18q deletions: Report on a new affected child and follow-up on the original reported familial cases. Am J Med Genet 43: 535-538.
Cody JD, Sebold C, Malik A, Heard P, Carter E, Crandall A, Soileau B, Semrud-Clikeman M, Cody CM, Hardis LJ, Li J, Lancaster J, Fox PT, Stratton RF, Perry B, Hale DE (2007). Recurrent Interstitial Deletions of Proximal 18q. A New Syndrome Involving Expressive Speech Delay. Am J Med Genet 143A: 1181-1190.
Krasikov N, Thompson K, Sekhon GS (1992). Monosomy 18q12.1-21.1: A recognizable syndrome? Report of a patient and review of the literature. Am J Med Genet 43: 531-534.
McEntagart M, Carey A, Breen C, McQuaid S, Stallings RL, Green AJ, King MD (2001). Molecular characterization of a proximal chromosome 18q deletion. J Med Genet 38: 128-129.
Poissonnier M, Turleau C, Oliver-Martin M, Milleret-Proyart M, Prieur M, Dubois M, Cabanis M, Mugneret F, Blanc P, Noel L (1992). Interstitial deletion of the proximal region of the long arm of chromosome 18, del(18q12) a distinct clinical entity? A report of two new cases. Ann Genet 35(3): 146-51.
Schinzel A, Binkert F, Lillington DM, Sands M, Stocks RJ, Lindenbaum RH, Matthews H, Sheridan H (1991). Interstitial deletion of the long arm of chromosome 18, del(18)(q12.2q21.1): A report of three cases of an autosomal deletion with mild phenotype. J Med Genet 28:352-355.
Surh LC, Ledbetter DH, Greenberg F (1991). Interstitial deletion of chromosome 18[del(18)(q11.2q12.2 or q12.2q21.1)]. Am J Med Genet 41:15-17.
Tinkle BT, Christianson CA, Schorry EK, Webb T, Hopkin RJ (2003). Long-term survival in a patient with del(18)(q12.2q21.1). Am J Med Genet 119A: 66-70.
Wilson MG, Towner JW, Forsman I, Siris E (1979). Syndromes associated with deletion of the long arm of chromsoome 18[del(18q)]. Am J Med Genet 3: 155-174.
Wilson GN, Al Saadi AA (1989). Obesity and abnormal behaviour associated with interstitial deletion of chromosome 18 (q12.2q21.1). J Med Genet 26: 62-63.