NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

15q Duplication Syndrome and Related Disorders

, MS, LGC, , BS, , MD, , PhD, , MD, , PhD, , MD, , PhD, , PhD, , MD, PhD, , MD, PhD, , DO, MSPH, , DPhil, , BS, PT, and , MD.

Author Information

Initial Posting: .

Estimated reading time: 26 minutes


Clinical characteristics.

15q duplication syndrome and related disorders (dup15q) are caused by presence of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms:

  • A maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~80% of cases);
  • A maternal interstitial 15q11.2-q13.1 duplication that typically includes one extra copy of 15q11.2-q13.1 within chromosome 15, resulting in trisomy for 15q11.2-q13.1 (~20% of cases).

Dup15q is characterized by hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms. Rarely, dup15q may also be associated with psychosis or sudden unexplained death. Those with maternal idic(15) are typically more severely affected than those with an interstitial duplication.


The diagnosis of dup15q is established by detection of at least one extra maternally derived copy of the PWACR, a region approximately 5 Mb long within chromosome 15q11.2-q13.1.


Treatment of manifestations: It is suggested that a multidisciplinary team evaluate infants for motor and speech development and later assist in referrals for appropriate educational programs. Supportive care may include: occupational and physical therapy, alternative and augmentative communication, behavioral therapy (e.g., applied behavioral analysis therapy), psychotropic medications for behavioral manifestations, and standard management for seizures.

Surveillance: Periodic: neurodevelopmental and/or developmental/behavioral assessments, and monitoring for evidence of seizures and/or change in seizure type.

Agents/circumstances to avoid: Seizure triggers (e.g., sleep deprivation, stress) and failure to follow medication regimen.

Evaluation of relatives at risk: Consider genetic testing of sibs of a proband (known to be at increased risk for an inherited maternal interstitial 15q11.2-q13.1 duplication) in order to refer those with the interstitial duplication promptly for multidisciplinary team evaluation.

Genetic counseling.

Dup15q caused by:

  • Maternal idic(15) has been de novo in all affected individuals reported to date; thus, risk to sibs is low, but presumed to be marginally greater than in the general population because of the possibility of maternal germline mosaicism;
  • Maternal interstitial 15q11.2-q13.1 duplication has been de novo in 85% of probands and inherited from the mother in 15%. If the mother has the 15q interstitial duplication, the risk to each child of inheriting the duplication is 50%.

Prenatal testing or preimplantation genetic diagnosis using chromosomal microarray (CMA) will detect the 15q interstitial duplication; however, prenatal test results cannot reliably predict the severity of the phenotype even in a pregnancy known to be at increased risk for dup15q.

GeneReview Scope

15q Duplication Syndrome and Related Disorders: Included Genetic Mechanisms
  • Maternal isodicentric 15q11.2-q13.1 supernumerary chromosome [idic(15)] resulting in tetrasomy or hexasomy for 15q11.2-q13.1
  • Maternal interstitial 15q11.2-q13.1 duplication or triplication

For synonyms and outdated terms see Nomenclature.


No formal diagnostic criteria have been published for 15q duplication syndrome and related disorders (referred to in this GeneReview as dup15q).

Suggestive Findings

15q duplication syndrome and related disorders (dup15q) should be suspected in individuals with the following:

  • Moderate to severe hypotonia in infancy and motor delays
  • Developmental delay, which can manifest as intellectual disability (ID) and/or speech and language delays
  • Autism spectrum disorder (ASD)
  • Seizures, particularly infantile spasms

Also seen frequently in individuals with dup15q:

Establishing the Diagnosis

The diagnosis of 15q duplication syndrome and related disorders (dup15q) is established by detection of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR), a region approximately 5 Mb long within chromosome 15q11.2-q13.1.

The proximal 15q region includes five regions of segmental duplications or low copy repeats (designated by breakpoints [BPs]), which result in increased susceptibility to genomic rearrangements [Hogart et al 2010]. These five regions are termed BP1 through BP5. The PWACR lies between BP2 and BP3 (Figure 1) and is always included in the interstitial duplications or the idic(15) that cause dup15q. The PWACR is imprinted: maternally derived increases in copy number cause dup15q (the topic of this GeneReview) while paternally derived increases are typically associated with more variable and sometimes different neurodevelopmental phenotypes (see Genetically Related Disorders) [Cook et al 1997, Urraca et al 2013].

Figure 1. A.

Figure 1

A. Schematic of the normal paternal and maternal chromosome 15 B. & C. The most common causes of dup15q:

The extra copy or copies of the PWACR most commonly arise by one of two mechanisms (Figure 1):

For this GeneReview, the disorder commonly known as dup15q is defined as the presence of one or more extra copies of 15q11.2-q13.1 that include the PWACR at the approximate position of 23651570-28664979 in the reference genome (NCBI Build GRCh37/hg19, seen here). Duplications may vary in size and have been seen up to 12 Mb long (as seen here) but must contain the PWACR to be causative of dup15q.

Although several genes of interest (e.g., ATP10A, CYFIP1, MAGEL2, NECDIN, SNRPN, UBE3A, snoRNAs, and a cluster of genes encoding GABAA receptor subunits) are within the 4.5- to 12-Mb recurrent duplication, no single gene that – when duplicated – causes dup15q has been identified (see Molecular Genetics for genes of interest in the duplicated region).

Genomic testing methods that determine the copy number of sequences can include chromosomal microarray analysis (CMA) or targeted duplication analysis. Note: (1) Interstitial 15q11.2-q13.1 duplications cannot typically be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques; however, idic(15) and large interstitial duplications (>5 Mb) that extend beyond the PWACR can be identified through cytogenetic analysis. (2) Mosaicism has been reported for idic(15) suggesting some degree of mitotic instability [Wang et al 2008], which may affect the phenotype and the sensitivity of genomic testing strategies used for diagnosis.

  • CMA using oligonucleotide arrays or SNP arrays can detect increases in copy number of the 15q11.2-q13.1 region in a proband. The ability to size the region involved depends on the type of microarray used and the density of probes in the 15q11.2-q13.1 region. CMA cannot reliably differentiate between idic(15) and interstitial triplication of 15q11.2-q13.1.
    Note: (1) Most individuals with dup15q are identified by CMA performed for the purpose of determining the cause of developmental delay, intellectual disability, or autism spectrum disorder. (2) FISH or a cytogenetic study is required to determine whether the duplication is supernumerary or interstitial and to determine whether there is evidence for mosaicism.
  • Targeted duplication analysis. FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA), or other targeted quantitative methods may be used to test relatives of a proband known to have the 15q11.2-q13.1 recurrent duplication.
    Note: (1) Targeted duplication testing is not appropriate for an individual in whom the 15q11.2-q13.1 recurrent duplication was not detected by CMA designed to target this region. (2) It is not possible to size the duplication routinely by use of targeted methods.

Parent of origin of the 15q11.2-q13.1 duplication is identified by either of the following:

Table 1.

Genomic Testing used in 15q Duplication and Related Disorders (dup15q)

Duplication 1ISCA ID 2Region Location 3MethodTest Sensitivity
ProbandAt-risk family members
4.5- to 12-Mb duplication at 15q11.2-q13.1 (includes PWACR)ISCA-37404 4 or ISCA-37478 5GRCh37/hg19 chr15: 21483759-32644465CMA 6, 7100%100%
Targeted duplication analysis 8Not applicable 9100%

See Molecular Genetics for details of the duplication and genes of interest in this region.


Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project (formerly the International Standards for Cytogenomic Arrays [ISCA] Consortium)


Genomic coordinates represent the minimum duplication size associated with the 15q11.2-q13.1 recurrent duplication as designated by ClinGen. Duplication coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the duplication as calculated from these genomic positions may differ from the expected duplication size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller duplications within this region may be clinically distinct from the 15q11.2-q13.1 recurrent duplication (see Genetically Related Disorders).


Class 1 duplication, approximately 6 Mb, extending from BP1 to BP3


Class 2 duplication, approximately 5 Mb, extending from BP2 to BP3


Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 15q11.2-q13.1 region. Note: 15q duplication and related disorders may not have been detectable by older oligonucleotide or BAC platforms.


FISH or cytogenetic analysis (e.g., G-banded chromosome study) should be completed as a follow up to CMA in most cases in order to determine whether the duplication is interstitial or contained within a supernumerary chromosome. Although CMA results may indicate whether the duplication is interstitial, this is not common.


Targeted duplication analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods.


Targeted duplication analysis is not appropriate for diagnosis of an individual in whom the 15q11.2-q13.1 duplication was not detected by CMA designed to target this region.

Evaluating at-risk relatives. FISH, qPCR, or other quantitative methods of targeted duplication analysis can be used to identify the 15q11.2-q13.1 recurrent duplication in at-risk relatives of the proband.

  • Maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15). Familial occurrence has not been reported. Parental testing is not routinely indicated but can be considered on a case-by-case basis (see Genetic Counseling).
  • Maternal interstitial 15q11.2-q13.1 duplication. Parental testing is indicated as these duplications may be inherited from a mother with a paternally derived de novo or inherited duplication (see Genetic Counseling).

Clinical Characteristics

Clinical Description

15q duplication syndrome and related disorders (dup15q) are characterized by hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms. These clinical findings differ significantly between people with a maternal interstitial duplication and those with a maternal isodicentric supernumerary chromosome, or idic(15) (Table 2). Those with a maternal idic(15) are typically more severely affected than those with an interstitial duplication. However, severity varies even among individuals who have increased dosage by the same genetic mechanism. Some phenotypic features, such as ASD, are more consistently observed in individuals with a maternal idic(15) or large (>5-Mb) interstitial duplications that extend beyond the PWACR [Hogart et al 2010].

Table 2.

15q Interstitial Duplication and Idic(15): Comparison of Clinical Features

FeatureMaternal Interstitial DuplicationMaternal Isodicentric Supernumerary Chromosome
HypotoniaMild to moderateSevere
Developmental delay / intellectual disabilityModerateSevere
Autism spectrum disorder (ASD)≥50% 1, 2≥80% 1, 3, 4
Epilepsy~25% 5~65% 5

Hypotonia and motor skills. Hypotonia in newborns and infants with dup15q is associated with feeding difficulties and gross motor delays [Depienne et al 2009, Hogart et al 2010, Urraca et al 2013].

Although childhood hypotonia impairs motor development, most children achieve independent walking after age two to three years (younger in children with an interstitial duplication) [Dennis et al 2006, Depienne et al 2009, Orrico et al 2009, Hogart et al 2010, Piard et al 2010, Al Ageeli et al 2014].

A wide-based or ataxic gait is common [Bundey et al 1994]. Delays and persistent impairment in both fine and gross motor skills affect adaptive living skills and distinguish children with dup15q syndrome from children with nonsyndromic ASD [DiStefano et al 2016].

Developmental delay and intellectual disability. Developmental delay in early childhood is nearly universal. This can be more specifically diagnosed as intellectual disability after age five years.

Most children and adults with dup15q function in the moderate to severe range of intellectual disability; however, there is some variability, with a higher range of cognitive abilities seen in those with an interstitial duplication.

Speech and language development is particularly affected, with universal delays ranging from moderate to severe [Grammatico et al 1994, Borgatti et al 2001, Hogart et al 2010]. Some individuals exhibit echolalia, pronoun reversal, and stereotyped utterances, while others may lack functional speech [Battaglia et al 1997, Battaglia 2008].

Autism spectrum disorder (ASD). Most children and adults with dup15q meet criteria for ASD. Compared to other CNVs known to cause ASD, dup15q confers the greatest risk, with an odds ratio of 42.6 or higher [Malhotra & Sebat 2012, Moreno-De-Luca et al 2013]. Manifestations of ASD, particularly difficulties with social interaction, may increase from early to late childhood [Simon et al 2010].

Compared to children with nonsyndromic ASD, children with dup15q/ASD demonstrate a distinctive behavioral profile, including preserved responsive social smile and directed facial expressions towards others – features that may inform behavioral interventions [DiStefano et al 2016].

Epilepsy. More than half of individuals with dup15q have epilepsy, usually involving multiple seizure types including infantile spasms and myoclonic, tonic-clonic, absence, and focal seizures [Conant et al 2014]. Seizures most often begin between ages six months and nine years [Battaglia 2008].

Dup15q is one of the most common known causes of infantile spasms [Conant et al 2014]. Infantile spasms in dup15q often progress to Lennox Gastaut syndrome and other complex seizure patterns that may be difficult to control. As many as 40% of individuals with seizures present initially with infantile spasms; of this group, approximately 90% subsequently develop other seizure types. Alternatively, individuals with dup15q may present with focal seizures only.

Intractable epilepsy in dup15q may result in disabling secondary effects, including falls or developmental regression. This occurs in more than half of individuals with frequent, uncontrolled seizures or nonconvulsive status epilepticus [Battaglia et al 1997].

In a small study, children with epilepsy were found to have lower cognitive and adaptive function than those without epilepsy [DiStefano et al 2016].

Dysmorphic features. Minor dysmorphic features often reported in dup15q include flattened nasal bridge with a short upturned nose, long philtrum, anteverted nostrils, downslanting palpebral fissures, micrognathia, low-set ears, flat occiput, low forehead, high-arched palate, and full lips [Battaglia et al 1997, Borgatti et al 2001, Hogart et al 2010, Urraca et al 2013]. These features are typically subtle and may be missed in infancy.

Psychosis. Although maternal idic(15) has been reported in schizophrenia cohorts [Bassett 2011, Ingason et al 2011, Costain et al 2013, Rees et al 2014], psychosis is not a commonly ascertained comorbidity in dup15q – a finding that may reflect the difficulty of recognizing and diagnosing psychosis in individuals with low cognitive functioning and limited verbal skills. For instance, psychosis is a common comorbidity in Prader-Willi syndrome caused by uniparental disomy, which similarly involves a duplication of the maternally contributed 15q11.2-13.1 [Boer et al 2002, Vogels et al 2003, Bassett 2011]. These individuals tend to have higher cognitive and verbal abilities than individuals with dup15q. Conversely, with a high rate of ASD in dup15q, psychosis related to mood disorder may be misdiagnosed as schizophrenia.

Sudden unexpected death in epilepsy (SUDEP) occurs in a small but significant minority of individuals with dup15q [Devinsky 2011, Wegiel et al 2012]. In dup15q, these deaths almost always occur during sleep and most (though not all) have occurred in teenagers and young adults with epilepsy.

SUDEP also occurs in other neurodevelopmental disorders involving severe cognitive impairments and treatment-resistant epilepsy. The mechanism underlying SUDEP is not well understood; however, available evidence suggests that in most cases a tonic-clonic seizure is followed by a shutdown of brain function and cardio-respiratory arrest. SUDEP occurs in 9% of individuals with epilepsy; the rate of SUDEP in dup15q is unknown.


In maternal idic(15) penetrance is 100%; expressivity is variable.

In maternal interstitial 15q11.2-q13.1 duplication, although penetrance appears to be complete, some individuals may have such mild features as to appear unaffected, reflecting variable expressivity rather than true non-penetrance.

Penetrance is the same for males and females.


Terms used to refer to15q duplication syndrome and related disorders:

  • 15q11.2-q13.1 duplication syndrome
  • Dup15q syndrome
  • Inverted duplication 15 (inv dup15)
  • Partial trisomy 15
  • Isodicentric chromosome 15 syndrome [Idic(15)]
  • Supernumerary marker chromosome 15 (SMC15)
  • Partial tetrasomy 15q


Dup15q is one of the most common cytogenetic anomalies in persons with ASD.

Differential Diagnosis

Classic Rett syndrome is a neurodevelopmental disorder caused by mutation of the X-linked gene MECP2 [Chahrour & Zoghbi 2007]. Rett syndrome is primarily seen in females and assumed to be fatal in most males. Features of classic Rett syndrome include normal development in the first six to 18 months of life followed by developmental stagnation, rapid regression of skills across developmental domains, and stabilization. A hallmark feature of Rett syndrome is the replacement of purposeful hand use with repetitive, stereotypic hand movements. Additional features include bruxism (teeth grinding), disordered breathing, sleep disturbances, autistic features, seizures, and unprovoked crying or screaming.

Findings similar to those of 15q duplication syndrome and related disorders (dup15q) include motor and language impairments, autistic features, and seizures. However, individuals with dup15q:

  • Tend to show delays from early infancy and rarely have psychomotor regression in the absence of intractable epilepsy;
  • Do not have loss of purposeful hand movements or the behavioral phenotypes of Rett syndrome.

See MECP2 Disorders.

Pathogenic variants in CDKL5 (OMIM 300203), an X-linked gene, have been identified in (1) females with early-onset severe seizures who have poor cognitive development but little in the way of Rett syndrome-like features [Archer et al 2006, Bahi-Buisson et al 2008] and (2) males with severe-to-profound intellectual disability and early-onset intractable seizures [Elia et al 2008].

Individuals with dup15q and those with pathogenic CDKL5 variants can both present with severe cognitive delays, intellectual disability, and early-onset seizures; however, moderate-to-severe infantile hypotonia is more characteristic of dup15q.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with 15q duplication syndrome or related disorders (dup15q), the following evaluations are recommended:

  • Complete review of systems
  • Physical examination
  • Assessment of possible feeding difficulties associated with hypotonia
  • Neurologic examination including assessment for seizure activity and baseline EEG
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

A multidisciplinary team evaluation is recommended beginning in early infancy to evaluate motor and speech development and later to assist in referrals for appropriate educational programs.

Supportive care may include the following:

  • Occupational and physical therapy
  • Alternative and augmentative communication
  • Behavioral therapy (e.g., applied behavioral analysis therapy)
  • Psychotropic medications for behavioral manifestations
  • Standard management for seizures including medications, vagus nerve stimulators, and/or ketogenic diets [Conant et al 2014]. Effectiveness of antiepileptic drug (AED) treatment varies by seizure type and severity. No prospective or randomized-controlled data on AED therapy in dup15q have been published. See Conant et al [2014] for parent-reported effectiveness of various medications and treatments.

Seizure management is important in preventing secondary complications, including (in the most severe cases) brain damage, developmental regression, and sudden unexpected death in epilepsy (SUDEP) [Devinsky 2011].

Approximately half of seizure-related deaths are not due to SUDEP, but to other causes including status epilepticus, drowning, falls, and accidents. Many of these are preventable. For example, status epilepticus may be prevented with the use of rescue medications such as rectal diazepam or nasal midazolam. Some evidence suggests that prompt identification of a seizure and basic care (e.g., repositioning a person on the side instead of face down) after a seizure may help prevent SUDEP [Ryvlin et al 2013]. However, the only known preventive therapy is the best possible seizure control [Ryvlin et al 2011]. Although a variety of monitors can help detect SUDEP (e.g., wrist and mattress accelerometers), none can prevent it [Devinsky 2011].

Caregivers. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit (pdf).

Prevention of Secondary Complications

Ongoing pediatric care with regular immunizations is indicated.


The following are appropriate:

  • Periodic neurodevelopmental and/or developmental/behavioral assessments
  • Periodic monitoring for evidence of seizures and/or change in seizure type

Agents/Circumstances to Avoid

Seizure triggers (e.g., sleep deprivation, stress, and failure to follow medication regimen) should be avoided.

Evaluation of Relatives at Risk

Consider genetic testing of sibs of a proband who is known to have an inherited maternal interstitial 15q11.2-q13.1 duplication in order to refer sibs with an interstitial duplication promptly for developmental evaluation and early intervention services

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Currently, no clinical trials for dup15q exist. However, ongoing work regarding treatment in Angelman syndrome and autism spectrum disorder (ASD) may inform future treatments in dup15q.

Search in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Dup15q caused by a maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15) – has been de novo in all probands reported to date.

Dup15q caused by maternal interstitial 15q11.2-q13.1 duplication has been de novo in 85% and inherited from the mother in 15%.

Risk to Family Members

Maternal Isodicentric 15q11.2-q13.1 Supernumerary Chromosome – Idic(15)

Parents of a proband

  • Idic(15) has been de novo in all probands reported to date.
  • Parental testing is not routinely indicated. However, based on one report of maternal transmission of supernumerary partial trisomy of the region [Michelson et al 2011], suggestive clinical manifestations in a mother (epilepsy, ASD, schizophrenia, or other reported findings) should prompt consideration of parental testing.

Sibs of a proband. The risk to sibs appears to be low as the idic(15) is de novo in all affected individuals reported to date. However, because of the possibility of maternal germline mosaicism, the risk is presumed to be marginally greater than in the general population.

Offspring of a proband. Individuals with idic(15) are not known to reproduce.

Other family members. Given that all instances of idic(15) reported to date have been de novo, the risk to other family members is presumed to be low.

Maternal 15q Interstitial Duplication

Parents of a proband

  • To date, maternally derived 15q interstitial duplications have been de novo in approximately 85% of reported individuals and inherited in approximately 15%.
  • If the maternal 15q interstitial duplication found in the proband cannot be detected in maternal leukocyte DNA, the most likely explanation is a de novo 15q interstitial duplication in the proband.
  • Evaluation of the mother by genomic testing that will detect the 15q interstitial duplication present in the proband is recommended.
    Note: If the mother of a proband inherited a 15q interstitial duplication from her father (i.e., the maternal grandfather of the proband), the mother will not have dup15q syndrome. Instead, she may appear to be unaffected or have features associated with paternal duplications, which – although distinct from those of the proband – may share some similarities (see Genetically Related Disorders).

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the mother: if the mother of the proband has the 15q interstitial duplication, the risk to each sib of inheriting the duplication is 50%. However, it is not possible to reliably predict the severity of the phenotype of the individual.
  • If the maternal 15q interstitial duplication identified in the proband cannot be detected in maternal leukocyte DNA, the risk to sibs is presumed to be low as the 15q interstitial duplication is most likely de novo in the proband.

Offspring of a proband. Each child of an individual with a 15q interstitial duplication has a 50% chance of inheriting the duplication.

Other family members. The risk to other family members depends on the genetic status of the proband's parents: if a parent has the 15q interstitial duplication, his or her family members may also have the duplication.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. Similarly, decisions about testing to determine the genetic status of at-risk family members are best made before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are at risk of having a child with dup15q.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Maternal idic(15). Risk to future pregnancies is presumed to be low, as to date all reported instances of idic(15) have been de novo. However, couples may wish to consider prenatal testing or preimplantation genetic diagnosis as risk may be slightly greater than in the general population due to the possibility of parental germline mosaicism.

Maternal 15q interstitial duplication

  • Pregnancies known to be at increased risk for the 15q interstitial duplication. Prenatal testing or preimplantation genetic diagnosis using CMA that will detect the 15q interstitial duplication found in the proband may be offered when:
    • The mother has a paternally derived or inherited 15q interstitial duplication;
    • The parents do not have the duplication but have had a child with a 15q interstitial duplication. In this instance, the recurrence risk associated with the possibility of parental germline mosaicism or other predisposing genetic mechanisms is probably <1%.
  • Pregnancies not known to be at increased risk for idic(15) or a 15q interstitial duplication. CMA performed in a pregnancy not known to be at increased risk for dup15q may detect increased copy numbers of 15q11.2-q13.1 due to an interstitial duplication or idic(15).

Note: Prenatal test results cannot reliably predict the severity of the phenotype (see Clinical Description) whether the pregnancy is known or not known to be at increased risk for dup15q.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Dup15q Alliance
    PO Box 674
    Fayetteville NY 13066
    Phone: 855-DUP-15QA
  • Unique: The Rare Chromosome Disorder Support Group
    G1 The Stables
    Station Road West
    Oxted Surrey RH8 9EE
    United Kingdom
    Phone: +44 (0) 1883 723356
  • Dup15q Alliance International Registry
    PO Box 674
    Fayetteville NY 13066

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

15q Duplication Syndrome and Related Disorders: Genes and Databases

GeneChromosome LocusProteinClinVar
Not applicable15q11.2-q13.1Not applicable

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for 15q Duplication Syndrome and Related Disorders (View All in OMIM)


Molecular Pathogenesis

The extra copy or copies of the PWACR most commonly arise by one of two mechanisms (Figure 1):

The proximal 15q region includes five regions of segmental duplications or low copy repeats (designated by breakpoints [BPs]), which result in increased susceptibility to genomic rearrangements [Robinson et al 1993, Robinson et al 1998, Christian et al 1999]. These five regions are termed BP1 through BP5. The Prader-Willi/Angelman critical region (PWACR) lies between BP2 and BP3 (Figure 1) and is always included in the interstitial duplications or the idic(15) that cause dup15q. Duplications that extend from BP1 to BP3 are referred to as Class I duplications; those that span BP2 and BP3 only are Class II duplications. The PWACR is imprinted: maternally derived increases in copy number cause dup15q while paternally derived increases are typically associated with more variable and sometimes different neurodevelopmental phenotypes [Cook et al 1997, Urraca et al 2013].

The maternal isodicentric 15q11.2-q13.1 – or idic(15) – is typically a bisatellited chromosome thought to arise from U-type exchange during meiosis. Idic(15), which typically includes two mirrored copies of 15pter-q13.1 (p arm of chromosome 15, centromere, and 15q11.2-q13.1) [Roberts et al 2003], is sometimes referred to as inv dup (15). The distal breakpoint is typically BP3 (approximate position [hg19] 28800000) on both sides of truly isodicentric chromosomes and BP4 and BP5 (approximate positions [hg19] 30700000 and [hg19] 32500000) for asymmetric supernumerary chromosomes (Figure 2) [Hogart et al 2010]. Idic(15) usually results in tetrasomy for 15q11.2-q13.1.

Figure 2.

Figure 2.

Asymmetry in dup15q, as seen in: A. Interstitial triplication of 15q11.2-13.1; and

Interstitial duplications leading to dup15q arise by nonallelic homologous recombination (NAHR) between two different breakpoint regions (e.g., BP1 and BP3). The distal breakpoint for maternal interstitial duplications is typically BP3 (approximate position [hg19] 28812406), and the proximal breakpoint is typically either BP1 or BP2 (approximate positions [hg19] 22964304 or [hg19] 23966600, respectively). Interstitial duplications usually result in trisomy for 15q11.2-q13.1.

Variations of these primary mechanisms include the following:

  • Interstitial 15q11.2-q13.1 triplication, which results in tetrasomy of 15q11.2-q13.1. This phenotype tends to be more severe than that of maternal interstitial 15q11.2-q13.1 duplication and more like that of maternal isodicentric 15q11.2-q13.1 supernumerary chromosome [Ungaro et al 2001, Hogart et al 2010] (Figure 3).
  • Isodicentric 15q hexasomy. The phenotype is severe, including profound intellectual disability, intractable epilepsy, and more prominent dysmorphic features (myopathic facies and low-set ears) [Mann et al 2004] (Figure 3).
  • Asymmetric isodicentric or interstitial maternal triplications, which typically result in tetrasomy for 15q11.2-q13.2 and trisomy for 15q13.2-13.3. These asymmetric copy number variations are observed in approximately 10%-15% of isodicentric and interstitial chromosomes [Dup15q Alliance International Registry, 3-14-14] (Figure 2).
  • Ring chromosome 15. Rarely, supernumerary ring chromosomes that include the PWACR have been seen. These are typically mosaic, indicating the unstable nature of ring chromosomes [Wang et al 2008].
Figure 3.

Figure 3.

Uncommon variations in copy number seen in dup15q A. Interstitial triplication of 15q11.2-13.1

Genes of interest in this region


Literature Cited

  • Al Ageeli E, Drunat S, Delanoë C, Perrin L, Baumann C, Capri Y, Fabre-Teste J, Aboura A, Dupont C, Auvin S, El Khattabi L, Chantereau D, Moncla A, Tabet AC, Verloes A. Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases. Eur J Med Genet. 2014;57:5–14. [PubMed: 24239951]
  • Archer HL, Whatley SD, Evans JC, Ravine D, Huppke P, Kerr A, Bunyan D, Kerr B, Sweeney E, Davies SJ, Reardon W, Horn J, MacDermot KD, Smith RA, Magee A, Donaldson A, Crow Y, Hermon G, Miedzybrodzka Z, Cooper DN, Lazarou L, Butler R, Sampson J, Pilz DT, Laccone F, Clarke AJ. Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. J Med Genet. 2006;43:451–6. [PMC free article: PMC2564520] [PubMed: 16183801]
  • Bahi-Buisson N, Nectoux J, Rosas-Vargas H, Milh M, Boddaert N, Girard B, Cances C, Ville D, Afenjar A, Rio M, Héron D, N'guyen Morel MA, Arzimanoglou A, Philippe C, Jonveaux P, Chelly J, Bienvenu T. Key clinical features to identify girls with CDKL5 mutations. Brain. 2008;131:2647–61. [PubMed: 18790821]
  • Bassett AS. Parental origin, DNA structure, and the schizophrenia spectrum. Am J Psychiatry. 2011;168:350–3. [PMC free article: PMC3276592] [PubMed: 21474594]
  • Battaglia A. The inv dup (15) or idic(15) syndrome (Tetrasomy 15q). Orphanet J Rare Dis. 2008;3:30. [PMC free article: PMC2613132] [PubMed: 19019226]
  • Battaglia A, Gurrieri F, Bertini E, Bellacosa A, Pomponi MG, Paravatou-Petsotas M, Mazza S, Neri G. The inv dup(15) syndrome: a clinically recognizable syndrome with altered behavior, mental retardation and epilepsy. Neurology. 1997;48:1081–6. [PubMed: 9109904]
  • Battaglia A., Parrini B., Tancredi R. The behavioural phenotype of idic(15) syndrome. Am J Med Genet Part C Semin Med Genet. 2010;154C:448–55. [PubMed: 20981774]
  • Boer H, Holland A, Whittington J, Butler J, Webb T, Clarke D. Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet. 2002;359:135–6. [PubMed: 11809260]
  • Borgatti R, Piccinelli P, Passoni D, Dalprà L, Miozzo M, Micheli R, Gagliardi C, Balottin U. Relationship between clinical and genetic features in "inverted duplicated chromosome 15" patients. Pediatr Neurol. 2001;24:111–6. [PubMed: 11275459]
  • Bundey S, Hardy C, Vickers S, Kilpatrick MW, Corbett JA. Duplication of the 15q11-13 region in a patient with autism, epilepsy and ataxia. Dev Med Child Neurol. 1994;36:736–42. [PubMed: 8050626]
  • Burnside RD, Pasion R, Mikhail FM, Carroll AJ, Robin NH, Youngs EL, Gadi IK, Keitges E, Jaswaney VL, Papenhausen PR, Potluri VR, Risheg H, Rush B, Smith JL, Schwartz S, Tepperberg JH, Butler MG. Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Hum Genet. 2011;130:517–28. [PMC free article: PMC6814187] [PubMed: 21359847]
  • Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009;17:3–13. [PMC free article: PMC2985966] [PubMed: 18781185]
  • Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007;56:422–37. [PubMed: 17988628]
  • Chaste P, Sanders SJ, Mohan KN, Klei L, Song Y, Murtha MT, Hus V, Lowe JK, Willsey AJ, Moreno-De-Luca D, Yu TW, Fombonne E, Geschwind D, Grice DE, Ledbetter DH, Lord C, Mane SM, Martin DM, Morrow EM, Walsh CA, Sutcliffe JS, State MW, Martin CL, Devlin B, Beaudet AL, Cook EH Jr, Kim SJ. Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11.2, specifically breakpoints 1 to 2. Autism Res. 2014;7:355–62. [PMC free article: PMC6003409] [PubMed: 24821083]
  • Christian SL, Fantes JA, Mewborn SK, Huang B, Ledbetter DH. Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11-q13). Hum Mol Genet. 1999;8:1025–37. [PubMed: 10332034]
  • Conant KD, Finucane B, Cleary N, Martin A, Muss C, Delany M, Murphy EK, Rabe O, Luchsinger K, Spence SJ, Schanen C, Devinsky O, Cook EH, LaSalle J, Reiter LT, Thibert RL. A survey of seizures and current treatments in 15q duplication syndrome. Epilepsia. 2014;55:396–402. [PubMed: 24502430]
  • Cook EH Jr, Lindgren V, Leventhal BL, Courchesne R, Lincoln A, Shulman C, Lord C, Courchesne E. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet. 1997;60:928–34. [PMC free article: PMC1712464] [PubMed: 9106540]
  • Costain G, Lionel AC, Merico D, Forsythe P, Russell K, Lowther C, Yuen T, Husted J, Stavropoulos DJ, Speevak M, Chow EWC, Marshall CR, Scherer SW, Bassett AS. Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays. Hum Mol Genet. 2013;22:4485–501. [PMC free article: PMC3889806] [PubMed: 23813976]
  • Cox DM, Butler MG. The 15q11.2 BP1-BP2 microdeletion syndrome: a review. Int J Mol Sci. 2015;16:4068–82. [PMC free article: PMC4346944] [PubMed: 25689425]
  • Dagli A, Buiting K, Williams CA. Molecular and Clinical Aspects of Angelman Syndrome. Mol Syndromol. 2012;2:100–12. [PMC free article: PMC3366701] [PubMed: 22670133]
  • DeLorey TM, Handforth A, Anagnostaras SG, Homanics GE, Minassian BA, Asatourian A, Fanselow MS, Delgado-Escueta A, Ellison GD, Olsen RW. Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. J Neurosci. 1998;18:8505–14. [PMC free article: PMC6792844] [PubMed: 9763493]
  • DeLorey TM, Sahbaie P, Hashemi E, Homanics GE, Clark JD. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder. Behav Brain Res. 2008;187:207–20. [PMC free article: PMC2684890] [PubMed: 17983671]
  • Dennis NR, Veltman MW, Thompson R, Craig E, Bolton PF, Thomas NS. Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. Am J Med Genet A. 2006;140:434–41. [PubMed: 16470730]
  • Depienne C, Moreno-De-Luca D, Heron D, Bouteiller D, Gennetier A, Delorme R, Chaste P, Siffroi JP, Chantot-Bastaraud S, Benyahia B, Trouillard O, Nygren G, Kopp S, Johansson M, Rastam M, Burglen L, Leguern E, Verloes A, Leboyer M, Brice A, Gillberg C, Betancur C. Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders. Biol Psychiatry. 2009;66:349–59. [PubMed: 19278672]
  • Devinsky O. Sudden, unexpected death in epilepsy. N Engl J Med. 2011;365:1801–11. [PubMed: 22070477]
  • DiStefano C, Gulsrud A, Huberty S, Kasari C, Cook E, Reiter L, Thibert R, Jeste SS. Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome. J Neurodev Disord. 2016;8:19. [PMC free article: PMC4858912] [PubMed: 27158270]
  • Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. Neurology. 2008;71:997–9. [PubMed: 18809835]
  • Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, Game RM, Rudd DS, Zurawiecki D, McDougle CJ, Davis LK, Miller J, Posey DJ, Michaels S, Kolevzon A, Silverman JM, Bernier R, Levy SE, Schultz RT, Dawson G, Owley T, McMahon WM, Wassink TH, Sweeney JA, Nurnberger JI, Coon H, Sutcliffe JS, Minshew NJ, Grant SF, Bucan M, Cook EH, Buxbaum JD, Devlin B, Schellenberg GD, Hakonarson H. Autism genome-wide copy number variation reveal ubiquitin and neuronal genes. Nature. 2009;459:569–73. [PMC free article: PMC2925224] [PubMed: 19404257]
  • Grammatico P, Di Rosa C, Roccella M, Falcolini M, Pelliccia A, Roccella F, Del Porto G. Inv dup(15): contribution to the clinical definition of phenotype. Clin Genet. 1994;46:233–7. [PubMed: 7820937]
  • Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME. The Angelman Syndrone protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 2010;140:704–16. [PMC free article: PMC2843143] [PubMed: 20211139]
  • Harlalka GV, Baple EL, Cross H, Kühnle S, Cubillos-Rojas M, Matentzoglu K, Patton MA, Wagner K, Coblentz R, Ford DL, Mackay DJ, Chioza BA, Scheffner M, Rosa JL, Crosby AH. Mutation of HERC2 causes developmental delay with Angelman-like features. J Med Genet. 2013;50:65–73. [PubMed: 23243086]
  • Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM. 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet. 2007;16:691–703. [PMC free article: PMC1934608] [PubMed: 17339270]
  • Hogart A, Wu D, LaSalle JM, Schanen NC. The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13. Neurobiol Dis. 2010;38:181–91. [PMC free article: PMC2884398] [PubMed: 18840528]
  • Ingason A, Kirov G, Giegling I, Hansen T, Isles AR, Jakobsen KD, Kristinsson KT, le Roux L, Gustafsson O, Craddock N, Möller HJ, McQuillin A, Muglia P, Cichon S, Rietschel M, Ophoff RA, Djurovic S, Andreassen OA, Pietiläinen OP, Peltonen L, Dempster E, Collier DA, St Clair D, Rasmussen HB, Glenthøj BY, Kiemeney LA, Franke B, Tosato S, Bonetto C, Saemundsen E, Hreidarsson SJ., GROUP Investigators. Nöthen MM, Gurling H, O'Donovan MC, Owen MJ, Sigurdsson E, Petursson H, Stefansson H, Rujescu D, Stefansson K, Werge T. Maternally derived microduplications at 15q11-q13: Implication of imprinted genes in psychotic illness. Am J Psychiatry. 2011;168:408–17. [PMC free article: PMC3428917] [PubMed: 21324950]
  • Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST, Richard G, Compton JG, Fuller AE, Gliem TJ, Huang S, Collinson MN, Beal SJ, Ackley T, Pickering DL, Golden DM, Aston E, Whitby H, Shetty S, Rossi MR, Rudd MK, South ST, Brothman AR, Sanger WG, Iyer RK, Crolla JA, Thorland EC, Aradhya S, Ledbetter DH, Martin CL. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med. 2011;13:777–84. [PMC free article: PMC3661946] [PubMed: 21844811]
  • Kirov G, Rees E, Walters JTR, Escott-Price V, Georgieva L, Richards AL, Chambert KD, Davies G, Legge SE, Moran JL, McCarroll SA, O'Donovan MC, Owen MJ. The penetrance of copy number variations for schizophrenia and developmental delay. Biol Psychiatry. 2014;75:378–85. [PMC free article: PMC4229045] [PubMed: 23992924]
  • Lowther C, Costain G, Stavropoulos DJ, Melvin R, Silversides CK, Andrade DM, So J, Faghfoury H, Lionel AC, Marshall CR, Scherer SW, Bassett AS. Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature. Genet Med. 2015;17:149–57. [PMC free article: PMC4464824] [PubMed: 25077648]
  • Malhotra D, Sebat J. CNVs: Harbingers of a rare variant revolution in psychiatric genetics. Cell. 2012;148:1223–41. [PMC free article: PMC3351385] [PubMed: 22424231]
  • Mann SM, Wang NJ, Liu DH, Wang L, Schultz RA, Dorrani N, Sigman M, Schanen NC. Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanismfor partial hexasomy. Hum Genet. 2004;115:104–11. [PubMed: 15141347]
  • Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER, Ravan SA, Abramson RK, Wright HH, Delong GR, Cuccaro ML, Pericak-Vance MA, Gilbert JR. Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet. 2001;15:245–59. [PubMed: 12092907]
  • Michelson M, Eden A, Vinkler C, Leshinsky-Silver E, Kremer U, Lerman-Sagie T, Lev D. Familial partial trisomy 15q11-13 presenting as intractable epilepsy in the child and schizophrenia in the mother. Eur J Paediatr Neurol. 2011;15:230–3. [PubMed: 21145272]
  • Miller DT, Shen Y, Weiss LA, Korn J, Anselm I, Bridgemohan C, Cox GF, Dickinson H, Gentile J, Harris DJ, Hegde V, Hundley R, Khwaja O, Kothare S, Luedke C, Nasir R, Poduri A, Prasad K, Raffalli P, Reinhard A, Smith SE, Sobeih MM, Soul JS, Stoler J, Takeoka M, Tan WH, Thakuria J, Wolff R, Yusupov R, Gusella JF, Daly MJ, Wu BL. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009;46:242–8. [PMC free article: PMC4090085] [PubMed: 18805830]
  • Moreno-De-Luca D, Sanders SJ, Willsey AJ, Mulle JG, Lowe JK, Geschwind DH, State MW, Martin CL, Ledbetter DH. Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts. Mol Psychiatry. 2013;18:1090–5. [PMC free article: PMC3720840] [PubMed: 23044707]
  • Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, Inoue K, Tomonaga S, Watanabe Y, Chung YJ, Banerjee R, Iwamoto K, Kato T, Okazawa M, Yamauchi K, Tanda K, Takao K, Miyakawa T, Bradley A, Takumi T. Abnormal behavior in a chromosome-engineered mouse model for human 15q11–13 duplication seen in autism. Cell. 2009;137:1235–46. [PMC free article: PMC3710970] [PubMed: 19563756]
  • Orrico A, Zollino M, Galli L, Buoni S, Marangi G, Sorrentino V. Late-onset Lennox-Gastaut syndrome in a patient with 15q11.2-q13.1 duplication. Am J Med Genet A. 2009;149A:1033–5. [PubMed: 19396834]
  • Piard J, Philippe C, Marvier M, Beneteau C, Roth V, Valduga M, Béri M, Bonnet C, Grégoire MJ, Jonveaux P, Leheup B. Clinical and molecular characterization of a large family with an interstitial 15q11q13 duplication. Am J Med Genet A. 2010;152A:1933–41. [PubMed: 20635369]
  • Puffenberger EG, Jinks RN, Wang H, Xin B, Fiorentini C, Sherman EA, Degrazio D, Shaw C, Sougnez C, Cibulskis K, Gabriel S, Kelley RI, Morton DH, Strauss KA. A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Hum Mutat. 2012;33:1639–46. [PubMed: 23065719]
  • Rees E, Walters JTR, Georgieva L, Isles AR, Chambert KD, Richards AL, Mahoney-Davies G, Legge SE, Moran JL, McCarroll SA, O'Donovan MC, Owen MJ, Kirov G. Analysis of copy number variations at 15 schizophrenia-associated loci. Br J Psychiatry. 2014;204:108–14. [PMC free article: PMC3909838] [PubMed: 24311552]
  • Roberts SE, Maggouta F, Thomas NS, Jacobs PA, Crolla JA. Molecular and fluorescence in situ hybridization characterization of the breakpoints in 46 large supernumerary marker 15 chromosomes reveals an unexpected level of complexity. Am J Hum Genet. 2003;73:1061–72. [PMC free article: PMC1180486] [PubMed: 14560400]
  • Robinson WP, Dutly F, Nicholls RD, Bernasconi F, Penaherrera M, Michaelis RC, Abeliovich D, Schinzel AA. The mechanisms involved in formation of deletions and duplications of 15q11-q13. J Med Genet. 1998;35:130–6. [PMC free article: PMC1051217] [PubMed: 9580159]
  • Robinson WP, Spiegel R, Schinzel AA. Deletion breakpoints associated with the Prader-Willi and Angelman syndromes (15q11-q13) are not sites of high homologous recombination. Hum Genet. 1993;91:181–4. [PubMed: 8462978]
  • Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol. 2011;10:961–8. [PubMed: 21937278]
  • Ryvlin P, Nashef L, Tomson T. Prevention of sudden unexpected death in epilepsy: a realistic goal? Epilepsia. 2013;54 Suppl 2:23–8. [PubMed: 23646967]
  • Samaco RC, Hogart A, LaSalle JM. Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet. 2005;14:483–92. [PMC free article: PMC1224722] [PubMed: 15615769]
  • Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, Murtha MT, Bal VH, Bishop SL, Dong S, Goldberg AP, Jinlu C, Keaney JF III, Klei L, Mandell JD, Moreno-De-Luca D, Poultney CS, Robinson EB, Smith L, Solli-Nowlan T, Su MY, Teran NA, Walker MF, Werling DM, Beaudet AL, Cantor RM, Fombonne E, Geschwind DH, Grice DE, Lord C, Lowe JK, Mane SM, Martin DM, Morrow EM, Talkowski ME, Sutcliffe JS, Walsh CA, Yu TW., Autism Sequencing Consortium. Ledbetter DH, Martin CL, Cook EH, Buxbaum JD, Daly MJ, Devlin B, Roeder K, State MW. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron. 2015;87:1215–33. [PMC free article: PMC4624267] [PubMed: 26402605]
  • Simon EW, Haas-Givler B, Finucane B. A longitudinal follow-up study of autistic symptoms in children and adults with duplications of 15q11-13. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:463–7. [PubMed: 19548260]
  • Ungaro P, Christian SL, Fantes JA, Mutirangura A, Black S, Reynolds J, Malcolm S, Dobyns WB, Ledbetter DH. Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14. J Med Genet. 2001;38:26–34. [PMC free article: PMC1734721] [PubMed: 11134237]
  • Urraca N, Cleary J, Brewer V, Pivnick EK, McVicar K, Thibert RL, Schanen NC, Esmer C, Lamport D, Reiter LT. The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature. Autism Res. 2013;6:268–79. [PMC free article: PMC3884762] [PubMed: 23495136]
  • Urraca N, Davis L, Cook EH, Schanen NC, Reiter LT. A single-tube quantitative high-resolution melting curve method for parent-of-origin determination of 15q duplications. Genet Test Mol Biomarkers. 2010;14:571–6. [PMC free article: PMC3064527] [PubMed: 20642357]
  • van Bon BW, Mefford HC, Menten B, Koolen DA, Sharp AJ, Nillesen WM, Innis JW, de Ravel TJ, Mercer CL, Fichera M, Stewart H, Connell LE, Ounap K, Lachlan K, Castle B, Van der Aa N, van Ravenswaaij C, Nobrega MA, Serra-Juhé C, Simonic I, de Leeuw N, Pfundt R, Bongers EM, Baker C, Finnemore P, Huang S, Maloney VK, Crolla JA, van Kalmthout M, Elia M, Vandeweyer G, Fryns JP, Janssens S, Foulds N, Reitano S, Smith K, Parkel S, Loeys B, Woods CG, Oostra A, Speleman F, Pereira AC, Kurg A, Willatt L, Knight SJ, Vermeesch JR, Romano C, Barber JC, Mortier G, Pérez-Jurado LA, Kooy F, Brunner HG, Eichler EE, Kleefstra T, de Vries BB. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet. 2009;46:511–23. [PMC free article: PMC3395372] [PubMed: 19372089]
  • Vanlerberghe C, Petit F, Malan V, Vincent-Delorme C, Bouquillon S, Boute O, Holder-Espinasse M, Delobel B, Duban B, Vallee L, Cuisset JM, Lemaitre MP, Vantyghem MC, Pigeyre M, Lanco-Dosen S, Plessis G, Gerard M, Decamp M, Mathieu M, Morin G, Jedraszak G, Bilan F, Gilbert-Dussardier B, Fauvert D, Roume J, Cormier-Daire V, Caumes R, Puechberty J, Genevieve D, Sarda P, Pinson L, Blanchet P, Lemeur N, Sheth F, Manouvrier-Hanu S, Andrieux J. 15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: a series of 52 patients. Eur J Med Genet. 2015;58:140–7. [PubMed: 25596525]
  • Vogels A, Matthijs G, Legius E, Devriendt K, Fryns J. Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome. J Med Genet. 2003;40:72–73. [PMC free article: PMC1735257] [PubMed: 12525547]
  • Wang NJ, Parokonny AS, Thatcher KN, Driscoll J, Malone BM, Dorrani N, Sigman M, LaSalle JM, Schanen NC. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15. BMC Genet. 2008;9:2. [PMC free article: PMC2249594] [PubMed: 18177502]
  • Wegiel J, Schanen NC, Cook EH, Sigman M, Brown WT, Kuchna I, Nowicki K, Wegiel J, Imaki H, Yong Ma S, Marchi E, Wierzba-Bobrowski T, Chauhan A, Chauhan V, Cohen IL, London E, Flory M, Lach B, Wisnewski T. Differences between the pattern of developmental abnormalities in autism associated with duplications 15q11.2-q13 and idiopathic autism. J Neuropathol Exp Neurol. 2012;71:382–97. [PMC free article: PMC3612833] [PubMed: 22487857]
  • Wolpert CM, Menold MM, Bass MP, Qumsiyeh MB, Donnelly SL, Ravan SA, Vance JM, Gilbert JR, Abramson RK, Wright HH, Cuccaro ML, Pericak-Vance MA. Three probands with autistic disorder and isodicentric chromosome 15. Am J Med Genet. 2000;96:365–72. [PubMed: 10898916]
  • Zhou D, Gochman P, Broadnax DD, Rapoport JL, Ahn K. 15q13.3 duplication in two patients with childhood-onset schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2016;171:777–83. [PMC free article: PMC5069586] [PubMed: 26968334]
  • Ziats MN, Goin-Kochel RP, Berry LN, Ali M, Ge J, Guffey D, Rosenfeld JA, Bader P, Gambello MJ, Wolf V, Penney LS, Miller R, Lebel RR, Kane J, Bachman K, Troxell R, Clark G, Minard CG, Stankiewicz P, Beaudet A, Schaaf CP. The complex behavioral phenotype of 15q13.3 microdeletion syndrome. Genet Med. 2016;18:1111–8. [PubMed: 26963284]
  • Zielinski C, Müller C, Smolen J. Use of plasmapheresis in therapy of systemic lupus erythematosus: a controlled study. Acta Med Austriaca. 1988;15:155–8. [PubMed: 3064527]

Chapter Notes


The authors are indebted to the Dup15q Alliance for its efforts to advance research into dup15q. Many thanks go to Christa L Martin, PhD, Geisinger Health System, for technical assistance in the preparation of this review.

Revision History

  • 16 June 2016 (bp) Review posted live
  • 23 September 2015 (ll) Original submission
Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source ( and copyright (© 1993-2020 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK367946PMID: 27308687


Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...