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Disease Profile

8p inverted duplication/deletion syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

8p inverted duplication and deletion; Inverted 8p duplication/deletion syndrome; Invdupdel(8p)

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 96092

Definition
8p inverted duplication/deletion [invdupdel(8p)] syndrome is a rare chromosomal anomaly characterized clinically by mild to severe intellectual deficit, severe developmental delay (psychomotor and speech development), hypotonia with tendency to develop progressive hypertonia and severe orthopedic problems over time, minor facial anomalies and agenesis of the corpus callosum.

Epidemiology
Around 50 known cases have been reported. Prevalence is estimated at 1/22,000 to 1/30,000 births.

Clinical description
Most common clinical manifestations include developmental delay, mild to severe degree of cognitive deficit, lack or delay of expressive speech and language and hypotonia contributing to a severe psychomotor delay. Most children with invdupdel(8p) have been reported to be happy natured, sociable and communicative albeit non-verbal, but some may exhibit attention deficits, impulsivity and hyperactivity. Thirty to fifty percent of individuals with invdupdel(8p) have autism which varies greatly between individuals from very mild to severely autistic. Facial dysmorphism, more noticeable in childhood, are subtle and frequently include a prominent forehead, temporal baldness, anteverted nostrils, eversion of the lower lip, large mouth and ears and a short neck. Adults with invdupdel(8p) are normal to exceptionally tall and have a tendency to develop progressive hypertonia, spastic quadriplegia and severe orthopedic problems like contracted joints and scoliosis. Cardiac defects, eye abnormalities, urinary system anomalies, precocious puberty, high palate and abnormal dental development, as well as anomalies of extremities and dislocated hips have occasionally been reported.

Etiology
An inverted duplication with a terminal deletion of the short arm of chromosome 8 mostly occurs as either an inverted duplication from centromere to D8S552 with a pter deletion from D8S349 or as an inverted duplication from 8p11.2 or 8p21 to D8S552, with a telomeric deletion from D8349. The input of the 8p deletion to the clinical picture appears less significant than the 8p inversion duplication rearrangement. To date, all invdupdel(8p) have occurred de novo.

Diagnostic methods
Diagnosis is based on clinical manifestations and agenesis of the corpus callosum on brain magnetic resonance imaging (MRI) leading to chromosomal analysis. Molecular techniques may be used for the genetic characterization of the deletion (FISH, MLPA, CGH array).

Differential diagnosis
Differential diagnosis includes other multiple congenital anomalies/intellectual deficit syndromes such as Trisomy 8p (see this term), in particular those with a 8p21-p22 duplication.

Antenatal diagnosis
Antenatal diagnosis is based on echographic detection of fetal abnormalities (e.g. agenesis of corpus callosum) and cytogenetic analysis after amniocenteses or chorionic villus sampling.

Genetic counseling
Genetic counseling is recommended. Invdupdel(8p) rearrangements occur de novo. However, parents can carry a harmless common inversion involving the 8p23.1 segment (prevalence 1/4 to 1/5) which on rare occasions might lead to the more complex invdupdel(8p) rearrangement in their offspring.

Management and treatment
There is no specific medical treatment. Physiotherapy from an early age as well as occupational therapy and speech therapy are recommended. Some patients benefit from music therapy. No gross orthopedic complications are noted. However, regular follow-up is needed.

Prognosis
There is no report on life expectancy. The majority of invdupdel(8p) individuals will need lifelong full-time care. Spastic quadriplegia may be slowly progressive with age.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of chromosome segregation
0002916
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Frontal balding
0002292
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Macrotia
Large ears
0000400
Pectus excavatum
Funnel chest
0000767
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Severe global developmental delay
0011344
Spastic tetraplegia
0002510
Wide mouth
Broad mouth
Large mouth

[ more ]

0000154
30%-79% of people have these symptoms
Agenesis of corpus callosum
0001274
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Autism
0000717
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Impulsivity
Impulsive
0100710
Long fingers
0100807
Long philtrum
0000343
Positional foot deformity
0005656
Progressive spastic paraplegia
0007020
Round face
Circular face
Round facial appearance
Round facial shape

[ more ]

0000311
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Abnormality of dental eruption
Abnormality of tooth eruption
0006292
Aplasia/Hypoplasia of the gallbladder
Absent/small gallbladder
Absent/underdeveloped gallbladder

[ more ]

0011466
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Contractures of the large joints
0005781
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dandy-Walker malformation
0001305
Dextrocardia
Heart tip and four chambers point towards right side of body
0001651
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Hydronephrosis
0000126
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Micropenis
Short penis
Small penis

[ more ]

0000054
Preauricular skin tag
0000384
Precocious puberty
Early onset of puberty
Early puberty

[ more ]

0000826
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Scoliosis
0002650
Seizure
0001250
Short neck
Decreased length of neck
0000470
Small hypothenar eminence
0010487
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Tetralogy of Fallot
0001636

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Unique – Rare Chromosome Disorder Support Group is a source of information and support to families and individuals affected by rare chromosome disorders. Click on the link to view information about 8p inverted duplication/deletion syndrome.

        In-Depth Information

        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.