Chromosome 22q13.1 Duplication Syndrome

December 31, 2014

Overview

A duplication of Chromosome 22q13 is a very rare genetic condition in which the cells of the body have a small but variable amount of extra genetic material from one of the body’s 46 chromosomes – chromosome 22. Like most other chromosome disorders, having an extra part of chromosome 22 may increase the risk of birth defects, developmental delay and intellectual disability. However, there is individual variation.

Source: Unique

Symptoms

Every person with a 22q13 duplication is unique and so each person will have different medical and developmental concerns. Additionally, no one person will have all of the features listed in this guide. However a number of common features have emerged:

Learning (intellectual) difficulties
Growth retardation, both in the womb and after birth
Failure to thrive
Motor delay
Floppiness or hypotonia
Microcephaly
Unusual facial features
Minor genital anomalies in boys

Causes

De novo 22q12/13 duplications are thought to be caused by a change that occurred when the parents’ sperm or egg cells formed or possibly during copying of the early cells after the egg and sperm joined.

One way that a deletion and a duplication could theoretically arise during the formation of egg or sperm cells. On the left are two matching chromosomes, each split to the centromere and ready to pair and exchange segments. The shaded bars show similar sequences of DNA in the chromosome that enable correct pairing

Prevention

Whether the duplication is inherited or de novo, what is certain is that as a parent there is nothing you did to cause the 22q13 duplication and nothing you could have done would have prevented it from occurring in your baby. No dietary, workplace or lifestyle factors are known to cause these chromosome changes. No one is to blame when this occurs and nobody is at fault and there is no reason for anyone to feel guilty.

Diagnosis

Sitting, moving, walking (gross motor skills):

Children with 22q12/13 duplications are typically slow to reach their developmental motor milestones.

Communication and Speech:

As with learning there is a great deal of variability depending on the region of 22q12/13 that is duplicated, but speech is delayed in many children and a few do not master language and continue to use gestures, facial expressions and vocal noises to indicate their needs and express their feelings.

Pregnancy and birth:

Many mothers carrying babies with 22q12/13 duplications experienced no pregnancy problems, had a normal delivery and only discovered their baby was affected after the birth. However, two babies were described as having intrauterine growth retardation (IUGR). This is a term used to describe babies whose growth in the womb has slowed, resulting in babies that are smaller than expected for the number of weeks of pregnancy

Newborn:

Babies with a 22q12/13 duplication are often, but not always, small and underweight at birth with an average birth weight of 2.94 kg (6lb 8oz). The range of birth weights is between 1.3 kg (2lb 14oz) and 4.48 kg (9lb 14oz). However, half (5/10) had a low birth weight (below 2.6 kilos or 5lb 12oz). Typically babies with a duplication of 22q12/3 are floppy (hypotonic) in the newborn period. This can result in delay reaching the baby developmental milestones (such as sitting, rolling, crawling and walking) and also cause feeding problems.

Feeding and Growth:

For those with a duplication of 22q12/13, feeding difficulties are a major area of concern for families, particularly as babies usually start out small and underweight.

After birth, babies tend to grow more slowly than their peers, with a small minority of babies described as ‘failure to thrive’. This term is used to describe a baby who has poor weight gain and physical growth failure over a period of time. The hypotonia that is common in babies with a 22q12/13 duplication can lead to difficulties with sucking and swallowing, and/or latching onto the breast. Babies with a cleft or high palate can also find the action of sucking and swallowing difficult. Three babies had a gastrostomy tube (a G-tube, feeding direct into the stomach) in order to meet their nutritional needs. One of these babies began taking a bottle during the day and using the G-tube at night. At 11 months the G-tube was removed and at her first birthday party she was able to enjoy birthday cake

Appearance:

You and the doctors may notice that your baby has slightly unusual facial features.

He or she may bear a resemblance to other babies and children with a 22q12/13 duplication. Some babies have a small head with a short neck. They often have a prominent forehead, a wide nasal bridge and low set ears. They may have widely spaced eyes (hypertelorism) with an epicanthic fold (an extra fold of skin covering the inner corner of the eye)

Learning:

Learning difficulties and intellectual disabilities are common in children with a 22q12/13 duplication. There is individual variation and it seems that children with very small terminal duplications or small interstitial duplications may have mild or moderate learning difficulties. One child with a 22q13.3qter duplication has been assessed as having only a borderline learning difficulty. However, children with larger duplications are more likely to have severe learning difficulties and will need more support with learning, and the amount of support they need may be quite considerable.

Communication and Speech:

Development: hand-eye co-ordination and dexterity (fine motor skills) and self care:

Hypotonia can also affect fine motor skills in children with a 22q12/13 duplication and they may experience delay in learning to use their hands. The extent of the delay varies considerably between individuals with some children (generally those with smaller duplications) not affected at all. Others may take longer to reach for and grab toys and hold a bottle or cup. Children may experience delays in being able to self-feed and hold a pen to write or draw.

Cleft palate or lip:

In the medical literature a cleft palate (an opening in the roof of the mouth resulting from the palate not forming correctly during development) is reported in around a third (9/27) of babies. Two further babies were born with a high arched palate.

Two Unique children have a high arched palate but none has a cleft palate

Heart defects:

Various structural problems of the heart have been seen. The most common type of problem is a hole in the heart. The two types of holes are:

Atrial septal defects (ASDs) – holes in the muscular wall between the two filling parts of the heart. Some blood flows through from the left to the right side, increasing the amount of blood flowing to the lungs. Treatment depends on the type of defect, whether it closes spontaneously and its size.

Ventricular septal defect (VSDs) – holes in the wall between the two pumping chamber of the heart (ventricles). This allows blood to flow from the left to the right chamber, increasing the blood flow to the lungs.

Minor genital anomalies:

Minor anomalies of the genitals are common in babies with chromosome disorders, most often affecting boys. Cryptorchidism (undescended testes) has been noted in boys with a duplication of 22q12/13.

Genital anomalies have also been reported to affect girls. Two girls have hypoplastic (underdeveloped) labia and one has ovarian dysgenesis (inactive ovaries)

Kidney:

Two babies in the published medical literature were born with an ectopic kidney (where the kidney is located in an abnormal position). One Unique member had one kidney removed because it was covered in kidney cysts

Brain anomalies:

Two girls in the medical literature had brain imaging that showed agenesis of the corpus callosum (ACC). The corpus callosum is the largest connective pathway in the brain.

It is made up of more than 200 million nerve fibres that connect the left and right sides (hemispheres) of the brain. ACC is a birth defect in which the corpus callosum is partially or completely absent, resulting in poorly connected or disconnected brain hemispheres. Each hemisphere of the brain is specialised to control movement and feeling in the opposite half of the body, and each hemisphere specialises in processing certain types of information (such as language or spatial patterns). Thus, to co-ordinate movement or to think about complex information, the hemispheres must communicate with each other. The corpus callosum is the main, although not the only, connector that allows that communication. The effects of ACC can be highly variable and in some children the ACC appears to have little obvious effect while others are more seriously affected (Biesecker 1995; Pramparo 2008).

Three Unique children have had brain imaging that showed no anomalies

Eyesight:

A squint (strabismus), where one or both eyes can turn inwards, outwards or upwards due to weakness of the muscles that control the eye, is the most common vision problem. Treatment of strabismus depends on the cause but can include patching the stronger eye, exercises, glasses to correct a refractive error such as long sight and surgery to realign the muscles that hold the eye in place.

A number of other vision problems have been reported to affect just one child. One child in the published medical literature had poor vision in both eyes and coloboma, a developmental defect in part of the structure of the eye, usually caused in the womb when the cleft that forms to help the nourishment of the developing eye does not close properly. Coloboma commonly affects the iris when it makes the pupil look like a keyhole. One child at Unique has poor focus and wears a patch for one hour every day. One Unique baby had a cataract (clouding of the eye’s lens) on one eye. One child has poor binocular vision

Hearing:

Children usually have normal hearing although a small number have hearing loss.

Two Unique children with a 22q12/13 duplication have a moderate hearing loss and wear a hearing aid. Two children in the medical literature (both with a 22q12 duplication) have been reported with hearing loss. Another child with a 22q13.1qter duplication has no hearing in her right ear

Feet:

Although not seen in any Unique members, club foot (talipes) has been reported in three children with large 22q12qter duplications in the medical literature. Treatment is individually tailored and aims to straighten the foot so that it can grow and develop normally.

Hands

Many children have hands that are unusual in some way. Unusual features vary quite a lot and are often just cosmetic – a single crease across the palm, an incurving fifth finger (clinodactyly) or fingers that are unusually short or very slender

Seizures:

Seizures have been reported in three children, one with a 22q13.2 duplication; one with a 22q13.3 duplication and one with an interstitial duplication of 22q13.1q13.2. Seizures have not been reported in any Unique members

Teeth:

Generally speaking, children with chromosome disorders have a somewhat higher rate of dental problems than other children. At the same time, some children can be quite resistant to having their teeth cleaned; this can be an issue with some children who take no food orally and do not strongly associate the mouthing experience with pleasure. One child in the medical literature has malocclusion (the teeth are not aligned properly)

Behaviour:

Children with a 22q12/3 duplication are typically happy, sociable, loving and affectionate. However, some children – although not all – have some behavioural issues. Hyperactivity has been described in three children described in the medical literature and one at Unique (all with a 22q13 duplication). One of these, a 10-year-old boy with a 22q13.1q13.2 duplication, has been diagnosed with attention deficit hyperactivity disorder (ADHD) which is characterised by restlessness and a short attention span, as well as a sleep disorder. Bipolar disorderwhich is characterized by mood swings and periods of aggressiveness alternating with periods of reduced initiative has been observed in some people. Other issues seen in only one child include oppositional behaviour, inappropriate friendliness to strangers and self-injurious behaviour

Sensory issues affect some children. One child does not like to eat certain textures and will gag when she eats them (Unique).

Behaviour within the autistic spectrum has been reported in one Unique child.

A diagnosis of autism can be extremely helpful in accessing services and tailoring the educational and behavioural therapy to meet the specific needs of a child with autism

Adults with a 22q12 or 22q13 duplication:

To date, there are very few adults known to have a 22q12 or 22q13 duplication. Unique has one adult member, a man of 23 years who has a severe learning difficulty and no speech or signing. Three adults have been described in the medical literature.

A 19-year-old man with an interstitial duplication of 22q12.1q13.1 has mild learning difficulties and good speech. He is clumsy with poor fine motor skills. A 27-year-old man with an interstitial duplication of 22q11.2q13.1 has a moderate learning disability

and needs help with daily living. He has lived in a long-stay centre for those with learning disabilities since he was 11 years old. A 40-year-old man with a 22q13.3qter duplication only discovered the duplication when he passed it on to his son. He has mild learning difficulties, no behavioural issues and works in a sheltered environment

Fertility:

As far as we are aware, only one person has been known to pass a duplication on to their child. A 40-year-old man (described above) passed a 22q13.3qter duplication on to his son. Neither has a speech impairment. The father has mild learning difficulties but his 4-year-old son has a moderate learning disability together with hyperactivity

Prognosis

The possibility of having another pregnancy with a 22q12/13 duplication depends on the parents’ chromosomes. If both parents have normal chromosomes when their blood cells are tested, the duplication is unlikely to happen again. However, if either parent has a chromosome inversion on one of their copies of chromosome 22 or carries a balanced translocation involving chromosome 22, the possibility is greatly increased of having other affected pregnancies.

Treatment

Since 22q deletion syndrome has the ability to affect every system of the body, it is important that affected children are treated by a team of pediatric specialists who can identify the variety of physical and psychosocial needs these patients may have. Although there is no cure for the 22q deletion, many therapies and medical interventions are available to help address its associated symptoms. The earlier these symptoms are detected, the more we can do to help. That’s why, when diagnosed with this condition, evaluation is recommended in some or all of the following areas. We will help you navigate through each step of your evaluation.

Resources

Parents should have the opportunity to meet a genetic counsellor to discuss their specific recurrence risks and options for prenatal and preimplantation genetic diagnosis (PGD). PGD requires the use of in vitro fertilisation and embryo biopsy, and only healthy embryos are transferred to the mother’s uterus. If the parents choose to conceive naturally, prenatal diagnosis options include chorionic villus sampling (CVS) and amniocentesis to test the baby’s chromosomes. Testing is generally very accurate, although not all of these tests are available in all parts of the world.