Chromosome 18 Syndromes

18번 염색체에 관해서 아래 5가지의 증후군이 있지만 각 증후군 내에서도 임상 소견이 매우 다양하다. 일부 환자에서는 특징적인 소견이 이들 증후군에 정확하게 일치할 수 있지만, 이들 임상정보가 환자의 수수께끼를 풀어가는 기나긴 과정의 출발점으로 작용할 수도 있다.

Normal Chromosome 18

18 p-

단완의 끝 부분이 떨어져 나간 형태


장완 끝 일부가 떨어져 나간 형태

Ring 18

단완과 장완의 끝 부분이 떨어져 나가 없어지고, 결실 부위끼리 결합하여 고리 모양(환상)을 만듬.

Tetrasomy 18p

염색체 한개가 추가된 양상인데, 추가염색체(extrachromosome)는 단완 한쌍이 중심절로 연결된 등완염색체(isochromosme) 형태임.

Trisomy 18

한쌍의 18번 염색체에 1개가 더 추가되어 3개의 염색체를 보임.

Chromosome 18 Registry and Research Society


The Deletion Syndromes of Chromosome 18


This information is intended to help parents understand chromosomal abnormalities in general and those relating to chromosome 18 specifically. It is hoped this information will help to clarify the basic principles of genetics and give a new perspective to parents about the information they may have already received.

These syndrome descriptions are the result of a search of the medical literature. They were derived from medical case reports written by physicians to inform other physicians. These reports are intended to aid in the recognition and diagnosis of the syndromes. A suspected diagnosis of a chromosomal abnormality involves the overall picture of the combination of characteristics. For this reason many seemingly inconsequential factors are mentioned such as an increased number of whorl patterns on the fingertips. It is the combination of characteristics and not so much the magnitude of each of them which is important in suspecting a chromosomal abnormality.

What is known about these syndromes is written primarily by diagnosticians,so there is very little information about the outcomes for the affected individual. What kind of speech problems do they have and how are they best dealt with? What kind of behavioral problems are seen and what treatments have worked best? What are their educational strengths and weaknesses?These are the kinds of questions that are important to parents, and these are the kind of questions that future editions of these syndrome descriptions will address as the Registry collects more of this kind of information.

To help understand these syndromes, we need to begin with some background information. Every cell in the human body contains within it, a complete set of instructions for carrying out every function that every kind of cell will ever need. Although a brain cell does not utilize the same instructions that a liver cell uses, they still contain the entire set of instructions. Just as a cookbook contains many recipes,some of which you rarely use. These instructions are the hereditary material and are packaged within each cell in 23 pairs of chromosomes. The complete set of instructions is called the genome. It is estimated that there are50,000-100,000 genes, or instructions, in the entire human genome. Chromosome18 is a small chromosome and contains only 1,000-2,000 genes. Thus far,only a handful have been identified.

There is one exception to the rule that every cell contains 23 pairs of chromosomes. These are the reproductive cells, or more specifically the egg and sperm cells. They each contain one-half of the normal number, or 23 chromosomes instead of 23 pairs. This means that the union of an egg and sperm cell will create a new cell with just the right amount of genetic material for a new person. You have inherited one chromosome of each pair,or half of your genetic material from each of your parents. Each of your children will inherit one of each pair from you.
   The abbreviated chemical name for the material that genes are made of is DNA. A chromosome is a single very long piece of DNA. The genes do not seem to be in any particular order on the chromosomes. For example, all the genes for making the skeletal system are not on one chromosome. This is why someone with a missing piece on one chromosome has problems with many different body systems. So finding out which genes are missing or extra in any one person with a chromosomal abnormality is very important in understanding their condition and ultimately being able to treat it.

Chromosomes can be looked at microscopically after they have been chemically stained. This procedure is called a karotype, and the cells used in this test are usually obtained from a blood sample. When the chromosomes are stained, they show a pattern of light and dark bands which is characteristic of each chromosome pair. Each chromosome pair also has a characteristic length, and each pair is assigned a number, with #1 being the longest and with #18 being one of the shortest. Each chromosome pair also has a characteristic constriction somewhere along its length,called the centromere. Since the centromere is not usually exactly in the middle, the chromosome looks as if the top part is shorter than the bottom.The top portion, or short arm is called "p" for petite and the bottom portion, or long arm is called "q". Using these three distinctions (relative length, banding patterns and location of the centromere),each pair of chromosomes can be reliably distinguished. The banding pattern is also utilized to provide reference landmarks along each chromosome.Below is a diagrammatic representation of the banding and therefore the numerical references of chromosome 18.

Chromosome 18The deletion syndromes of chromosome 18 include 18q-, 18p- and ring18.

This abnormalities of chromosome 18 are some of the most common of the autosomal deletion syndromes. Their combined frequency is estimated to be 1 in every 46,000 births. The deletion syndromes fall into 3 classes. First, 18p- (eighteen p minus), is any missing piece of the short arm of chromosome 18. Second, 18q- (eighteen q minus), is any missing piece of the long arm of chromosome 18. Third, Ring 18 is the joining of ends of the chromosome into a ring and results in missing material at each end of the chromosome.
Most deletions are terminal, meaning that the missing piece is from a breakpoint to the end of the chromosome. There are, however, a few people with interstitial deletions. This means that their missing piece is between two break points and a middle piece is missing. The exact size and placement of the deletion can vary and still be called 18p- or 18q- depending on which arm is involved. This variability is seen most often in 18q-. The result is, since the genes that are missing vary, the clinical picture varies as well. So a clear cut list of the symptoms is not always possible. There is yet another reason for the variation between individuals with the same syndrome. This is due to the fact that we each have two copies of each chromosome. Someone with a deletion syndrome, only has the deletion on one of the pair. The content of the normal chromosome can vary and will influence the development of the affected individual.

Most deletions arise as de novo events. Meaning that the deletion is anew one and occurred during the formation of the sperm or egg or very early in embryonic development. The parents of such a person have normal chromosomes and have a low probability of having another child with a chromosome abnormality.

Some cases result because one of the parents has a balanced translocation. This means that the parent has a deletion on one chromosome,but the deleted piece is attached to another chromosome. As a result, the parent still has all of his or her genetic information, although it is arranged is a different way. Therefore, this parent has no symptoms and probably had no idea that he or she has a chromosomal abnormality. A parent with a balanced translocation has a significant chance of having a child with missing or extra chromosomal material, and therefore of being an affected child. The reason parents have chromosome studies performed is to determine if one of them has a balanced translocation.

There are also cases in the literature in which a parent with one of these syndromes has a child also with the syndrome. Someone with one of these chromosomal abnormalities has a significant chance of having a child with the same abnormality. There is no evidence at this time that indicates that any of these syndromes can be caused by exposure to environmental agents, such as medications, x-rays or chemicals before or during pregnancy.
The following syndrome descriptions are the result of a search of the medical literature. There are several inherent problems with a compilation of other people's work. Not everyone mentions all of the same symptoms of the syndrome.If someone fails to mention that a patient has a high arched palate, is that because the patient did not have one, or because it was not noticed?Some features such as cleft lip are hard to miss and if present are most certainly reported. Some doctors may report that their patient has abnormal ears and another may state exactly what the deformity is, but there is no way of knowing if they are reporting the same abnormality. Therefore the frequency of each of these symptoms is not final, but instead represents the best information to date.

It is important to remember that it is usually the extreme or unusual cases which are reported, so the available information may produce a more severe picture of the syndrome. A diagnosis is usually only sought if the person has developmental or medical problems. A person who may look a little different and made it through school with C's and D's and actually has a chromosomal abnormality may never be diagnosed. It is also important to remember that these descriptions do not represent any single person.In fact, many parents report that their child has fewer than half of these problems. But a generalized description can still be useful to the parent who is searching for answers and trying to ask the right questions.

18q- Syndrome

The female to male ratio is 1.7/1. Birth weight averages 2800 gm (6 lb. 2 oz), which is below average but well within the normal range. Increased age of the parents does not appear to be a factor.

Features of the 18q- Syndrome

Characteristics % of Patients Characteristics % of Patients

Mental retardation*


Genu varum


Short stature (<5 percentile)


Up-slanting palpebral fissures


Flat midface


Low set ears






Prominent antihelix


Cleft lip


Abnormal male genitalia


Umbilical hernia




Nodules at corner of mouth


Carp mouth




Foot deformity




Atretic/stenotic ear canals


Inguinal hernia


Congenital heart disease


Large protruding forehead


Increased whorl patterns




Dysplastic labia minora


Dysplastic teeth


Long tapering digits


Delayed fontanel closure


Proximally placed thumbs






Gap between 1st & 2nd toe


Palate abnormality


Low posterior hairline






    High arched


Strawberry birthmark on face


    Bifid uvula


Short neck


Epicanthal folds


Severe feeding problems


IgA deficient




Impaired hearing


The following have been seen
in single patients:




Middle ear hypoplasia


Pale optic disc


Brushfield spots


Skin dimples


Cervical rib


Broad nasal bridge


Extra rib


Simian crease


Stubby fingers


Abnormal placement of 2nd toe










Horseshoe kidney


Thin hair




Widely spaced nipples




Fleshy tips of fingers






Absent kidney




Low IgM




Extraskelatal Ewing's sacroma




Cerebellar astrocytoma




Retinal cone rod dystrophy








Chronic granulomatous disease




Chronic arthritis




Steroid-17,20-Lyase deficiency


* most of the patients who were described as mentally retarded had no IQ score given. For those whose IQ was measured, the scores ranged from 5 to 88.
((References: Chasalow et al.,1986; Day et al. 1967; De Grouchy, 1969;Faed et al. 1972; Faulkner et al., 1983; Felding et al. 1987; Fujimotoet al., 1991; Hansen & Herlin, 1994; Insley 1967; Kushnick and Matsushita1968; Law and Masterson 1966; Miller et al. 1990; Naylor et al. 1978; Onoet al., 1994; Pagon et al 1979; Parker et al. 1972; Schinzel et al. 1975;Stewart and Bryant 1980; Stricker and Linker 1982; Subrt and Pokorny 1970;Summitt 1969; Vogel et al. 1990; Warburg,et al., 1991; Wertelecki and Gerald1971; Wilson et al. 1974)

The only progressive problem reported was tapetoretinal degeneration. It was seen in two unrelated patients age 10 and 49. This eye disease was thought to be the result of a small deletion at band 18q21. Therefore a person with a deletion in this region should be followed by an ophthalmologist.

A young child with 18q- will benefit from an early intervention program. Special services are available though the public school system for children at 3 years of age. Check with your local school district's Department of Special Education for details on the programs that they provide.The poor muscle tone will require years of physical and occupational therapy.The muscle tone problems, along with any hearing problems will probably delay speech and will require years of speech therapy. Mental function is highly variable, and if near normal may make services in special programs hard to obtain. It is recommended that a child with 18q- be seen at least once by the following specialists: a pediatric ophthalmologist, a pediatric neurologist, a developmental pediatrician, an otolaryngology, a pediatric endocrinologist and of course, a geneticist or genetic counselor of they have not already done so.

Here are some of our wonderful children who happen to have the 18q- syndrome.

Children with 18q- syndrome

18p- Syndrome

The female to male ratio is 2/1. Birth weight averages 2600 gm (5 lb. 11 oz.), which is the low end of normal. 19% died as newborns,all from severe brain malformations.

Features of the 18p- syndrome

Characteristic % of Patients The following features were seen in single cases:

Mental retardation *


Eccentric pupils (not in the center of the eye opening)

Short stature (below the 5th percentile)



Abnormal external ears
(low set, floppy and/or large)


High set thumbs

Holoprosencephaly **


Hip dislocation

IgA deficiency (an infection fighting agent)


Alopecia (permanent hair loss)

Small mandible (jaw)


Renal tubular defect (abnormal kidney function)

Excessive caries (cavities)


Amenorrhea (failure to menstruate)

Epicanthal folds (folds at inner edge of eye)


Rheumatoid arthritis

Short neck


Flat feet

Microcephaly (small head & brain)


Short limbs

Ptosis (droopy eyelids)



Hypotonia (poor muscle tone)


* Of those individuals whose IQ was measured,
the average was 59.

Strabismus (cross eyed)


** Holoprosencephaly is a developmental
malformation of the brain which has
a whole rage of severity, from a cyclops
malformation to a flat nasal bridge.
The frequency of these symptoms in the
entire 18p- population is listed below from
the most severe to the least severe.

Broad trunk


Webbed neck


Funnel chest




High palate


Abnormal toes


Cyclops (incompatible with life)


Widely spaced nipples


Cebocephaly (incompatible with life)


Clinodactyly (in-curved fingers or toes)


Arhinecephaly (incompatible with life)


Kyphosis (a spinal abnormality)


Cleft palate




Cleft lip




Hypotelorism (eyes too close)




Hypertelorism (eyes too far apart)




Single central front tooth




flat nasal bridge


(References: de Grouchy, 1969; Faust, et al., 1976; Finley,et al., 1972;Fischer, et al., 1970; Gorlin, et al.,1968; Leisti, et al., 1973; Levenson,et al.,1971; Moedjono, et al., 1979; Ruvalcaba & Thuline, 1969; Sabateret al., 1972; Schinzel et al., 1974; Schnabel & Hansen, 1983; Stofferet al., 1981; Subrt & Berankova, 1972; Taylor, et al., 1975; Uchida,et al., 1965; Vorsanova, et al., 1986; Weiss & Mayeda, 1969)

Of the 6 cases who have had autopsies (5 were newborns with severe holoprosencephaly, and 1 abortus), 3 had fissured or accessory spleens. The belief exists among geneticists that there are people with 18p- who are so mildly affected that they don't know that they have a chromosomal abnormality until they have a child who is also 18p-, and is more severely affected. While this may be true, there are no reports in the literature to substantiate this.

The developmental aspects of this disorder are even less well defined than for 18q-. Speech is often delayed and behavior problems such as inability to form relationships, have also been reported. Early intervention for young children and special education programs for those over 3, will probably be beneficial. These children should also be seen by a developmental pediatrician,pediatric neurologist, and of course a geneticist and genetic counselor.A person with 18p- should also be followed closely by a dentist.

Here are some of our wonderful children who happen to have the18p- syndrome.

Children with 18q- syndrome

The Ring 18 Syndrome

This syndrome results when the usually linear chromosome form a ring. Ring formation involves the breakage of the chromosome at both ends and the joining of the ends of the p and q arms back together.The amount of material lost from each arm of the chromosome can vary from so little that no symptoms of the corresponding syndrome are observed,to a significant part of one or both arms. Ring 18 can therefore appear to be like 18q- or 18p- or a combination of both. There are no unique features of this syndrome. The karyotype results should be able to detect a significant loss and therefore make a prediction on which symptoms to expect.


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