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Schizophrenia(SCZD)

MedGen UID:
48574
Concept ID:
C0036341
Mental or Behavioral Dysfunction
Synonyms: SCHIZOPHRENIA WITH OR WITHOUT AN AFFECTIVE DISORDER; SCZD
Modes of inheritance:
Heterogeneous
MedGen UID:
67020
Concept ID:
C0242960
Organism Attribute
Source: HPO
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Schizophrenic disorders (191526005); Schizophrenia (58214004)
 
Genes (locations): AKT1 (14q32.33); APOL2 (22q12.3); APOL4 (22q12.3); CHI3L1 (1q32.1); COMT (22q11.21); DAO (12q24.11); DAOA (13q33.2); DISC1 (1q42.2); DISC2 (1q42.2); DRD3 (3q13.31); DTNBP1 (6p22.3); HTR2A (13q14.2); MTHFR (1p36.22); RTN4R (22q11.21); SYN2 (3p25.2)
Related genes: SHANK3, NRXN1, SLC1A1, PRODH, NRG1
OMIM®: 181500
HPO: HP:0100753

Definition

Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target. [from GTR]

Additional descriptions

From Medical Genetics Summaries
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.  https://www.ncbi.nlm.nih.gov/books/NBK62008
From OMIM
Schizophrenia is a psychosis, a disorder of thought and sense of self. Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. There is no characteristic pathology, such as neurofibrillary tangles in Alzheimer disease (104300). Schizophrenia is a common disorder with a lifetime prevalence of approximately 1%. It is highly heritable but the genetics are complex. This may not be a single entity. Schizophrenia and bipolar disorder (see 125480) are generally considered to be separate entities, but patients who exhibit multiple symptoms of both disorders are often given the hybrid diagnosis schizoaffective disorder (Blacker and Tsuang, 1992). Genetic Heterogeneity of Schizophrenia with or without an Affective Disorder SCZD4 (600850) is associated with variation in the PRODH gene (606810); SCZD9 (604906) with variation in the DISC1 gene (605210); SCZD15 (613950) with variation in the SHANK3 gene (606230); SCZD16 (613959) with a chromosome duplication involving the VIPR2 gene (601970); SCZD17 (see 614332) with variation in the NRXN1 gene (600565); SCZD18 (615232) with variation in the SLC1A1 gene (133550); and SCZD19 (617629) with variation in the RBM12 gene (607179). For associations pending confirmation, see MAPPING and MOLECULAR GENETICS.  http://www.omim.org/entry/181500
From GHR
Schizophrenia is a mental health disorder classified as a psychosis, which means that it affects a person's thinking, sense of self, and perceptions. The disorder typically appears during late adolescence or early adulthood.Signs and symptoms of schizophrenia include false perceptions called hallucinations. Imaginary voices are the most common hallucinations in schizophrenia, but affected individuals can also experience imaginary visions, smells, or feelings of being touched. Strongly held false beliefs (delusions) are also characteristic of schizophrenia. For example, affected individuals may be certain that they are a particular historical figure or that they are being plotted against or controlled by others.People with schizophrenia often have decreased ability to function at school, at work, and in social settings. Disordered thinking and concentration, inappropriate emotional responses, erratic speech and behavior, and difficulty with personal hygiene and everyday tasks are also features of the disorder. People with schizophrenia may have diminished facial expression and animation (flat affect), and in some cases become unresponsive (catatonic). Substance abuse and suicidal thoughts and actions are common in people with schizophrenia.Certain movement problems such as tremors, facial tics, rigidity, and unusually slow movement (bradykinesia) or an inability to move (akinesia) are common in people with schizophrenia. In most cases these are side effects of medicines given to help control the disorder. However, some affected individuals exhibit movement abnormalities before beginning drug treatment.Some people with schizophrenia have mild impairment of intellectual function, but schizophrenia is not associated with the same types of brain changes that occur in people with dementias such as Alzheimer disease.Psychotic disorders such as schizophrenia are different from mood disorders, including depression and bipolar disorder, which primarily affect emotions. However, these disorders can occur together. Individuals who exhibit strong features of both schizophrenia and mood disorders are often given the hybrid diagnosis of schizoaffective disorder.  https://ghr.nlm.nih.gov/condition/schizophrenia

Clinical features

Delusions
MedGen UID:
3715
Concept ID:
C0011253
Mental or Behavioral Dysfunction
A belief that is pathological and is held despite evidence to the contrary.
Schizophrenia
MedGen UID:
48574
Concept ID:
C0036341
Mental or Behavioral Dysfunction
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Sensory hallucination
MedGen UID:
115982
Concept ID:
C0235153
Sign or Symptom
Perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and located in external objective space.
Social and occupational deterioration
MedGen UID:
356663
Concept ID:
C1866986
Finding

Conditions with this feature

DiGeorge sequence
MedGen UID:
4297
Concept ID:
C0012236
Disease or Syndrome
Individuals with 22q11.2 deletion syndrome (22q11.2DS) have a range of findings including the following: Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus). Palatal abnormalities (69%), particularly velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate. Characteristic facial features (present in the majority of individuals of northern European heritage). Learning difficulties (70%-90%). An immune deficiency (regardless of the clinical presentation) (77%). Additional findings include the following: Hypocalcemia (50%). Significant feeding and swallowing problems; constipation with or without structural gastrointestinal anomalies (intestinal malrotation, imperforate anus, and Hirschsprung disease). Renal anomalies (31%). Hearing loss (both conductive and sensorineural). Laryngotracheoesophageal anomalies. Growth hormone deficiency. Autoimmune disorders. Seizures (idiopathic or associated with hypocalcemia). CNS anomalies including tethered cord. Skeletal abnormalities (scoliosis with or without vertebral anomalies, clubbed feet, polydactyly, and craniosynostosis). Ophthalmologic abnormalities (strabismus, posterior embryotoxon, tortuous retinal vessels, scleracornea, and anophthalmia). Enamel hypoplasia. Malignancies (rare). Developmental delay (in particular delays in emergence of language), intellectual disability, and learning differences (non-verbal learning disability where the verbal IQ is significantly greater than the performance IQ) are common. Autism or autistic spectrum disorder is found in approximately 20% of children and psychiatric illness (specifically schizophrenia) is present in 25% of adults; however, attention deficit disorder, anxiety, perseveration, and difficulty with social interactions are also common.
Keratosis follicularis
MedGen UID:
5956
Concept ID:
C0022595
Disease or Syndrome
Darier-White disease, also known as keratosis follicularis, is an autosomal dominant skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead), palmoplantar pits, and distinctive nail abnormalities (Sakuntabhai et al., 1999). Onset is usually before the third decade, and penetrance is complete in adults, although expressivity is variable. Involvement may be severe, with widespread itchy malodorous crusted plaques, painful erosions, blistering, and mucosal lesions. Secondary infection is common. Sun, heat, and sweating exacerbate the symptoms. Darier disease never remits, but oral retinoids may reduce hyperkeratosis. Neuropsychiatric abnormalities, including mild mental retardation and epilepsy, have been described in association with Darier disease in a few families (Burge and Wilkinson, 1992); whether this is an association based on pleiotropism of the mutant gene or reflects coincidence is not clear. Histologic findings are (1) mild nonspecific perivascular infiltration in the dermis; (2) dermal villi protruding into the epidermis; (3) suprabasal detachment of the spinal layer leading to the formation of lacunae containing acantholytic cells; (4) in the more superficial epidermis, dyskeratotic round epidermal cells ('corps ronds'), the most distinctive feature; and (5) in the stratum corneum, 'grains' that resemble parakeratotic cells embedded in a hyperkeratotic horny layer. Electron microscopy reveals loss of desmosomal attachments, perinuclear aggregations of keratin filaments, and cytoplasmic vacuolization. Ultrastructural and immunologic studies suggest the disease results from an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.
Schizophrenia
MedGen UID:
48574
Concept ID:
C0036341
Mental or Behavioral Dysfunction
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.
Schizophrenia 1
MedGen UID:
65084
Concept ID:
C0220702
Disease or Syndrome
Schizophrenia 10
MedGen UID:
107776
Concept ID:
C0543918
Mental or Behavioral Dysfunction
Schizophrenia 4
MedGen UID:
371517
Concept ID:
C1833247
Disease or Syndrome
Schizophrenia 3
MedGen UID:
324936
Concept ID:
C1838069
Disease or Syndrome
Wolfram-like syndrome, autosomal dominant
MedGen UID:
387788
Concept ID:
C1857286
Autosomal dominant Wolfram-like syndrome is characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges (summary by Valero et al., 2008). Wolfram syndrome (WFS1; 222300) is an autosomal recessive allelic disorder characterized by optic atrophy, diabetes mellitus, hearing loss, and diabetes insipidus, and is caused by homozygous or compound heterozygous mutation in the WFS1 gene. An autosomal dominant syndrome involving optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy (125250), is caused by heterozygous mutation in the OPA1 gene (605290).
Chromosome 1q21.1 duplication syndrome
MedGen UID:
382715
Concept ID:
C2675891
Disease or Syndrome
1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1.Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention deficit hyperactivity disorder and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication.Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities.
1q21.1 recurrent microdeletion
MedGen UID:
393913
Concept ID:
C2675897
Congenital Abnormality
1q21.1 microdeletion is a chromosomal change in which a small piece of chromosome 1 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q21.1. This chromosomal change increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems. However, some people with a 1q21.1 microdeletion do not appear to have any associated features.About 75 percent of all children with a 1q21.1 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. The intellectual disability and learning problems associated with this genetic change are usually mild.Distinctive facial features can also be associated with 1q21.1 microdeletions. The changes are usually subtle and can include a prominent forehead; a large, rounded nasal tip; a long space between the nose and upper lip (philtrum); and a high, arched roof of the mouth (palate). Other common signs and symptoms of 1q21.1 microdeletions include an unusually small head (microcephaly), short stature, and eye problems such as clouding of the lenses (cataracts). Less frequently, 1q21.1 microdeletions are associated with heart defects, abnormalities of the genitalia or urinary system, bone abnormalities (particularly in the hands and feet), and hearing loss.Neurological problems that have been reported in people with a 1q21.1 microdeletion include seizures and weak muscle tone (hypotonia). Psychiatric or behavioral problems affect a small percentage of people with this genetic change. These include developmental conditions called autism spectrum disorders that affect communication and social interaction, attention deficit hyperactivity disorder (ADHD), and sleep disturbances. Studies suggest that deletions of genetic material from the 1q21.1 region may also be risk factors for schizophrenia.Some people with a 1q21.1 microdeletion do not have any of the intellectual, physical, or psychiatric features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have a relative with the chromosomal change. It is unknown why 1q21.1 microdeletions cause cognitive and physical changes in some individuals but few or no health problems in others, even within the same family.
Schizophrenia 15
MedGen UID:
462730
Concept ID:
C3151380
Disease or Syndrome
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., global developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural renal anomalies occur in 80% to 85% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: 10 to 50 years).

Professional guidelines

PubMed

National Collaborating Centre for Mental Health (UK)
Leicester (UK): British Psychological Society; 2009 Mar; PMID: 20704054Books & Documents

Recent clinical studies

Etiology

Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, Van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Mørch-Johnsen L, Faerden A, Flyckt L, Fatouros-Bergman H; Karolinska Schizophrenia Project Consortium (KaSP)., Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Preda A, De Rossi P, Piras F, Banaj N, Ciullo V, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S
Acta Psychiatr Scand 2017 May;135(5):439-447. Epub 2017 Mar 29 doi: 10.1111/acps.12718. PMID: 28369804Free PMC Article
Huang JH, Park H, Iaconelli J, Berkovitch SS, Watmuff B, McPhie D, Öngür D, Cohen BM, Clish CB, Karmacharya R
J Proteome Res 2017 Feb 3;16(2):481-493. Epub 2016 Nov 28 doi: 10.1021/acs.jproteome.6b00628. PMID: 28152600
Cropley VL, Klauser P, Lenroot RK, Bruggemann J, Sundram S, Bousman C, Pereira A, Di Biase MA, Weickert TW, Weickert CS, Pantelis C, Zalesky A
Am J Psychiatry 2017 Mar 1;174(3):286-295. Epub 2016 Dec 6 doi: 10.1176/appi.ajp.2016.16050610. PMID: 27919183
Klauser P, Baker ST, Cropley VL, Bousman C, Fornito A, Cocchi L, Fullerton JM, Rasser P, Schall U, Henskens F, Michie PT, Loughland C, Catts SV, Mowry B, Weickert TW, Shannon Weickert C, Carr V, Lenroot R, Pantelis C, Zalesky A
Schizophr Bull 2017 Mar 1;43(2):425-435. doi: 10.1093/schbul/sbw100. PMID: 27535082Free PMC Article
Liu D, Ji C, Zhuo K, Song Z, Wang Y, Mei L, Zhu D, Xiang Q, Chen T, Yang Z, Zhu G, Wang Y, Cheung EF, Xiang YT, Fan X, Chan RC, Xu Y, Jiang K
Aust N Z J Psychiatry 2017 Mar;51(3):270-277. Epub 2016 Jul 11 doi: 10.1177/0004867416640097. PMID: 27004487

Diagnosis

Ansari-Lari M, Farashbandi H, Mohammadi F
Trop Med Int Health 2017 Oct;22(10):1322-1327. Epub 2017 Aug 11 doi: 10.1111/tmi.12933. PMID: 28734096
Hoonakker M, Doignon-Camus N, Marques-Carneiro JE, Bonnefond A
Clin Neurophysiol 2017 Sep;128(9):1599-1607. Epub 2017 Jun 28 doi: 10.1016/j.clinph.2017.06.036. PMID: 28715711
Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Børglum AD, Gasse C
Am J Psychiatry 2017 Jul 1;174(7):686-694. Epub 2017 Jan 20 doi: 10.1176/appi.ajp.2016.16040442. PMID: 28103712
Cropley VL, Klauser P, Lenroot RK, Bruggemann J, Sundram S, Bousman C, Pereira A, Di Biase MA, Weickert TW, Weickert CS, Pantelis C, Zalesky A
Am J Psychiatry 2017 Mar 1;174(3):286-295. Epub 2016 Dec 6 doi: 10.1176/appi.ajp.2016.16050610. PMID: 27919183
Johnson EC, Bjelland DW, Howrigan DP, Abdellaoui A, Breen G, Borglum A, Cichon S, Degenhardt F, Forstner AJ, Frank J, Genovese G, Heilmann-Heimbach S, Herms S, Hoffman P, Maier W, Mattheisen M, Morris D, Mowry B, Müller-Mhysok B, Neale B, Nenadic I, Nöthen MM, O'Dushlaine C, Rietschel M, Ruderfer DM, Rujescu D, Schulze TG, Simonson MA, Stahl E, Strohmaier J, Witt SH; Schizophrenia Working Group of the Psychiatric Genomics Consortium., Sullivan PF, Keller MC
PLoS Genet 2016 Oct;12(10):e1006343. Epub 2016 Oct 28 doi: 10.1371/journal.pgen.1006343. PMID: 27792727Free PMC Article

Therapy

Catts SV, O'Toole B
Aust N Z J Psychiatry 2017 May;51(5):438-440. Epub 2017 Apr 4 doi: 10.1177/0004867417700278. PMID: 28374606
Huang JH, Park H, Iaconelli J, Berkovitch SS, Watmuff B, McPhie D, Öngür D, Cohen BM, Clish CB, Karmacharya R
J Proteome Res 2017 Feb 3;16(2):481-493. Epub 2016 Nov 28 doi: 10.1021/acs.jproteome.6b00628. PMID: 28152600
Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Børglum AD, Gasse C
Am J Psychiatry 2017 Jul 1;174(7):686-694. Epub 2017 Jan 20 doi: 10.1176/appi.ajp.2016.16040442. PMID: 28103712
Matosin N, Fernandez-Enright F, Lum JS, Newell KA
Neuropharmacology 2017 Mar 15;115:73-91. Epub 2015 Sep 6 doi: 10.1016/j.neuropharm.2015.08.003. PMID: 26349010
Kantrowitz JT, Epstein ML, Beggel O, Rohrig S, Lehrfeld JM, Revheim N, Lehrfeld NP, Reep J, Parker E, Silipo G, Ahissar M, Javitt DC
Brain 2016 Dec;139(Pt 12):3281-3295. doi: 10.1093/brain/aww262. PMID: 27913408

Prognosis

Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, Van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Mørch-Johnsen L, Faerden A, Flyckt L, Fatouros-Bergman H; Karolinska Schizophrenia Project Consortium (KaSP)., Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Preda A, De Rossi P, Piras F, Banaj N, Ciullo V, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S
Acta Psychiatr Scand 2017 May;135(5):439-447. Epub 2017 Mar 29 doi: 10.1111/acps.12718. PMID: 28369804Free PMC Article
Cropley VL, Klauser P, Lenroot RK, Bruggemann J, Sundram S, Bousman C, Pereira A, Di Biase MA, Weickert TW, Weickert CS, Pantelis C, Zalesky A
Am J Psychiatry 2017 Mar 1;174(3):286-295. Epub 2016 Dec 6 doi: 10.1176/appi.ajp.2016.16050610. PMID: 27919183
Liu D, Ji C, Zhuo K, Song Z, Wang Y, Mei L, Zhu D, Xiang Q, Chen T, Yang Z, Zhu G, Wang Y, Cheung EF, Xiang YT, Fan X, Chan RC, Xu Y, Jiang K
Aust N Z J Psychiatry 2017 Mar;51(3):270-277. Epub 2016 Jul 11 doi: 10.1177/0004867416640097. PMID: 27004487
Johnson EC, Bjelland DW, Howrigan DP, Abdellaoui A, Breen G, Borglum A, Cichon S, Degenhardt F, Forstner AJ, Frank J, Genovese G, Heilmann-Heimbach S, Herms S, Hoffman P, Maier W, Mattheisen M, Morris D, Mowry B, Müller-Mhysok B, Neale B, Nenadic I, Nöthen MM, O'Dushlaine C, Rietschel M, Ruderfer DM, Rujescu D, Schulze TG, Simonson MA, Stahl E, Strohmaier J, Witt SH; Schizophrenia Working Group of the Psychiatric Genomics Consortium., Sullivan PF, Keller MC
PLoS Genet 2016 Oct;12(10):e1006343. Epub 2016 Oct 28 doi: 10.1371/journal.pgen.1006343. PMID: 27792727Free PMC Article
Rohde PD, Demontis D, Cuyabano BC; Genomic Medicine for Schizophrenia Group., Børglum AD, Sørensen P
Genetics 2016 Aug;203(4):1901-13. Epub 2016 Jun 17 doi: 10.1534/genetics.116.189498. PMID: 27317683Free PMC Article

Clinical prediction guides

Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, Van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Mørch-Johnsen L, Faerden A, Flyckt L, Fatouros-Bergman H; Karolinska Schizophrenia Project Consortium (KaSP)., Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Preda A, De Rossi P, Piras F, Banaj N, Ciullo V, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S
Acta Psychiatr Scand 2017 May;135(5):439-447. Epub 2017 Mar 29 doi: 10.1111/acps.12718. PMID: 28369804Free PMC Article
MacDonald ML, Alhassan J, Newman JT, Richard M, Gu H, Kelly RM, Sampson AR, Fish KN, Penzes P, Wills ZP, Lewis DA, Sweet RA
Am J Psychiatry 2017 Jun 1;174(6):586-594. Epub 2017 Mar 31 doi: 10.1176/appi.ajp.2017.16070814. PMID: 28359200
Johnson EC, Bjelland DW, Howrigan DP, Abdellaoui A, Breen G, Borglum A, Cichon S, Degenhardt F, Forstner AJ, Frank J, Genovese G, Heilmann-Heimbach S, Herms S, Hoffman P, Maier W, Mattheisen M, Morris D, Mowry B, Müller-Mhysok B, Neale B, Nenadic I, Nöthen MM, O'Dushlaine C, Rietschel M, Ruderfer DM, Rujescu D, Schulze TG, Simonson MA, Stahl E, Strohmaier J, Witt SH; Schizophrenia Working Group of the Psychiatric Genomics Consortium., Sullivan PF, Keller MC
PLoS Genet 2016 Oct;12(10):e1006343. Epub 2016 Oct 28 doi: 10.1371/journal.pgen.1006343. PMID: 27792727Free PMC Article
Rohde PD, Demontis D, Cuyabano BC; Genomic Medicine for Schizophrenia Group., Børglum AD, Sørensen P
Genetics 2016 Aug;203(4):1901-13. Epub 2016 Jun 17 doi: 10.1534/genetics.116.189498. PMID: 27317683Free PMC Article
Srinivasan S, Bettella F, Mattingsdal M, Wang Y, Witoelar A, Schork AJ, Thompson WK, Zuber V; Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium., Winsvold BS, Zwart JA, Collier DA, Desikan RS, Melle I, Werge T, Dale AM, Djurovic S, Andreassen OA
Biol Psychiatry 2016 Aug 15;80(4):284-92. Epub 2015 Oct 21 doi: 10.1016/j.biopsych.2015.10.009. PMID: 26681495Free PMC Article

Recent systematic reviews

Catts SV, O'Toole B
Aust N Z J Psychiatry 2017 May;51(5):438-440. Epub 2017 Apr 4 doi: 10.1177/0004867417700278. PMID: 28374606
Walton E, Hibar DP, van Erp TG, Potkin SG, Roiz-Santiañez R, Crespo-Facorro B, Suarez-Pinilla P, Van Haren NE, de Zwarte SM, Kahn RS, Cahn W, Doan NT, Jørgensen KN, Gurholt TP, Agartz I, Andreassen OA, Westlye LT, Melle I, Berg AO, Mørch-Johnsen L, Faerden A, Flyckt L, Fatouros-Bergman H; Karolinska Schizophrenia Project Consortium (KaSP)., Jönsson EG, Hashimoto R, Yamamori H, Fukunaga M, Preda A, De Rossi P, Piras F, Banaj N, Ciullo V, Spalletta G, Gur RE, Gur RC, Wolf DH, Satterthwaite TD, Beard LM, Sommer IE, Koops S, Gruber O, Richter A, Krämer B, Kelly S, Donohoe G, McDonald C, Cannon DM, Corvin A, Gill M, Di Giorgio A, Bertolino A, Lawrie S, Nickson T, Whalley HC, Neilson E, Calhoun VD, Thompson PM, Turner JA, Ehrlich S
Acta Psychiatr Scand 2017 May;135(5):439-447. Epub 2017 Mar 29 doi: 10.1111/acps.12718. PMID: 28369804Free PMC Article
Liu W, Liu F, Xu X, Bai Y
Neurosci Lett 2017 Apr 24;647:122-128. Epub 2017 Mar 24 doi: 10.1016/j.neulet.2017.03.039. PMID: 28344127
Ding Y, Ju M, He L, Chen W
Comb Chem High Throughput Screen 2017;20(2):116-122. doi: 10.2174/1386207320666170117120828. PMID: 28124599
Catts VS, Lai YL, Weickert CS, Weickert TW, Catts SV
Biol Psychol 2016 Apr;116:57-67. Epub 2015 Nov 10 doi: 10.1016/j.biopsycho.2015.10.013. PMID: 26549579

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