8p inverted duplication and deletion - Inverted duplication & deletion of 8p Inverted duplication with

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  • rarechromo.orgrarechromo.orgrarechromo.orgrarechromo.org

    8p inverted

    duplication and

    deletion

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    Sources & References The information in this leaflet is drawn from the published medical literature and from Unique. At the time of compiling the information, Unique had 41 members with an inv dup 8p, 19 of them with a known deletion (see * page 3). Eighteen members completed a detailed questionnaire in 2004-5.

    References to information from Unique are marked U. For references from the medical literature, the first-named author and publication date are given to allow you to look for the abstracts or original articles on the internet in PubMed.

    Inverted duplication & deletion of 8p Inverted duplication with deletion of 8p, known as inv dup del 8p, is a rare genetic condition in which there is an extra copy of part of the genetic material that makes up the body’s chromosomes and a missing copy of another part of the genetic material. Like most other chromosome disorders, this does increase the risk of birth defects and developmental delay but the outcome for each baby is quite individual.

    The 46 chromosomes are the microscopically small structures in the nucleus of the body’s cells that carry genetic information. They are numbered in pairs from 1 to 22, running approximately from largest to smallest, with one member of each pair coming from the father and one from the mother, in addition to the sex chromosomes, X and Y for a boy and two Xs for a girl. Each chromosome has a short (p) arm, at the top in bright blue in the diagram below, and a long (q) arm. Chromosomes can be stained so that each has a distinctive pattern of light and dark bands when viewed at about 1000 times life size under a light microscope.

    One normal chromosome 8 and one chromosome 8 with inv dup del 8p

    Key to segments

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    In people with an inv dup del 8p, one chromosome 8 is normal (n(8) in the diagram on page 2) but there is an extra copy (blue in the diagram) of part of the short arm of the other chromosome 8. This is termed a duplication (dup for short). In addition, the end of the short arm of the other chromosome 8 (red in the diagram) is missing. This is termed deletion (del for short). The extra duplicated part runs in the opposite direction to normal and is therefore termed inverted (inv for short). See how the bands in the top blue section on the inv dup del(8) are the mirror image of those below the yellow band. The duplicated blue segments are separated by most of band 8p23.1 which remains neither duplicated nor deleted (coloured yellow in the diagram).

    The size of the duplicated (blue) section is not the same in all people with inv dup del 8p. In some it may be larger and in some smaller, depending on where the chromosome breaks to form the inv dup del 8 chromosome. The diagram illustrates a more common large form of the duplication with a breakpoint in band 8p11.22 (transition from black to blue as you move up the short arm in the diagram). In some people, however, the breakpoint is further up and the duplication correspondingly smaller.

    In around half the people with inv dup del 8ps, only the extra duplicated material is reported and not the small deletion * (see facing page). This is because the duplication is larger and easier to see and many cases were reported before the small deletion was discovered. However, it is currently believed that the great majority of people with inverted duplications of 8p have the small deletion as well (Guo 1995).

    The precise effects of gaining material from a chromosome vary depending on how large the duplication is, how many genes the duplication contains and what those genes do. The same principle applies to deletions. The effects may not be limited to the genes within a duplicated or deleted piece of chromosome because these genes may interact with other genes on the same chromosome or other chromosomes. In a child with inv dup del 8p, some children have brain anomalies as well as developmental delay with specific speech involvement and the large duplication is believed to cause this. Most, if not all, of the clinical features are caused by the duplication rather than the small deletion. We believe this because small deletions of the end of chromosome 8 have little if any effect when they are found on their own.

    How rare is inv dup del 8p?

    It is very rare, estimated to occur once in every 22,000 to 30,000 births.

    Around 50 children have been described in the medical literature

    (Floridia 1996;

    Giglio 2001;

    Masuda 2002).

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    Main features Features do vary between individuals but these have been found to be the most common and the most likely to make a difference to a child’s health or development. Facial features that are often similar among babies and children with inv dup del 8p are described in the Appearance section (page 6).

    • Developmental delay.

    • Some degree of learning disability.

    • Speech delay or absence.

    • Weakness or floppiness of the skeletal muscles (hypotonia).

    • Structural anomalies of the brain. Typically, this includes thinning or absence of the corpus callosum, a band of nerve fibres that connects the two sides of the brain. In some people the ventricles, the fluid-filled spaces within the brain, may be enlarged and the brain itself relatively small (see page 11).

    • Heart conditions at birth. Some small problems resolve naturally; others are corrected with surgery.

    Features that are not usually obvious at birth but may develop during childhood include:

    • Spinal curvature.

    • Contracted joints, making movement difficult.

    Other features Many other features have been noted in the medical literature. Some are known to be generally more common in children with chromosome disorders. Others may in fact be unconnected with the chromosome disorder. All the same, because they have occurred in other people with this chromosome disorder, you can expect your child’s paediatric specialists to be especially alert to them.

    • High palate.

    • Unusual dental development.

    • Eye abnormalities such as strabismus (squint) and iris coloboma, a developmental defect of the coloured part of the eye that gives it a ‘keyhole’ appearance. Underdevelopment of the eye, cataracts and developmental defects of the retina have also been observed. Some babies have a hooded upper eyelid (ptosis) on one side or both.

    • Anomalies of the arms, legs, hands or feet. A baby may have unusually angled feet, known as club foot (talipes). This can be corrected with therapy or surgery.

    • Hernias in the groin or the umbilicus.

    • Unusually positioned intestines.

    • Anomalies of the kidneys, urinary system and bladder.

    • Dislocated hips or hips that dislocate easily.

    • Early fusion of bone plates of the skull.

    • Precocious puberty. (Feldman 1993; de Die-Smulders 1995; Guo 1995; Tonk 2001).

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    First signs Signs may first be detected in pregnancy during ultrasound scanning. However, there is usually no obvious growth delay during pregnancy. Only the most severely affected babies are likely to be noticed and those with less obvious effects will not necessarily be identified until after birth. One baby in the Unique series was observed to have spina bifida, where part of the spinal cord is exposed through a gap in the backbone.

    Most frequently, babies in the Unique series were diagnosed when they missed their developmental milestones. No babies were diagnosed at birth with a congenital anomaly that had not been suspected during pregnancy, but one baby was diagnosed as a newborn after he had seizures and episodes where he stopped breathing . Three out of 16 babies were investigated because they had an unusual facial appearance (dysmorphic signs, see Appearance page 6) as well as developmental delay and hypotonia (de Die-Smulders 1995; Macmillin 2000; U).

    Families say …

    � I am a nurse and worked with syndrome children when I was studying. When M was born, I thought he had a syndrome-like appearance: a big, square forehead, a big mouth, a short neck, rather big ears with strange earlobes and an incurved fifth finger. His belly was big and he had a banana-shaped body, and he felt so ‘soft’ to hold on to. None of this was significant and the doctors on the maternity ward claimed that he was completely normal even when I said I was worried about him.

    � Initially R was investigated because of delays in walking and speech. But as we look back, there were other signs, one being that she was born with a full extra thumb, which we later learned is part of her del/dup.

    Pregnancy Information on pregnancy in the medical literature is sparse, but it is said that most babies are born at term. In the Unique series, seven out of 18 mothers went into premature labour between 32 and 36 weeks. Three mothers reported high blood pressure or pre-eclampsia and three babies were delivered by emergency Caesarean section. One mother, who went into premature labour at 35 weeks, had pregnancy bleeding between six and 12 weeks. Another had a placental abruption, where the placenta detaches from the wall of the uterus. Two mothers noticed very little fetal movement and one had very little amniotic fluid (oligohydramnios). Eight pregnancies were described as norm