Compiled up-to-date summaries of the most common Copy Number Variations (CNVs). To better understand the clinical variability of CNVs, the Prenatal Microarray Follow-up Study is working to study CNVs diagnosed in children prenatally by following those children over a three-year period.
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Ranging from moderate to severe, developmental delays and intellectual disabilities are among the most common features that have been noted in children testing positive for 1p36 deletions. Speech and language problems are common among these children, with about half of individuals affected by this deletion being completely non-verbal. Behavior problems are frequently noted and include poor social interaction, poor temper control and aggression issues, as well as repetitive movements. Furthermore, most children in this population have poor muscle tone (known as hypotonia) which contributes to the delays in development – in particular, learning to crawl, walk, and grasp items is hindered by the lack of muscle tone.
Among other health concerns associated with 1p36 deletions, seizures are one of the more frequently occurring concerns, with episodes of seizures reported in about half of this population of children. Some children have been found to have structural brain problems as well as congenital heart problems. There is also a potentially increased risk for kidney problems which include: reflux,hydronephrosis, kidney ectopia and kidney stones. Hearing loss, delayed bone age, scoliosis, rib anomalies and hypothyroidism have been seen.
Although facial features associated with the 1p36 deletion vary between individuals, most children have a distinctive appearance characterized by a smaller-than-average sized head, a larger- and rounder-than-average forehead, a pointed chin, a distinct ear shape, and a flat nasal bridge. These features can vary even between relatives, however.
The following rare occurrences have been reported: small spleen size, skin lesions of small blood vessels (known as telangiectasia), extra fingers or toes (known as polydactyly), restricted spinal canal (known as congenital spinal stenosis), rearrangement of the intestines (known as intestinal malrotation), narrowing of a section of the stomach (known as hypertrophic pyloric stenosis), malformation of the rectum (known as imperforate anus), and nerve tissue tumors (known as neuroblastoma).
Some common features noted in children testing positive for a 1q21.1 deletion include: smaller-than-average head-size (known as microcephaly), mild intellectual disability, mild to moderate developmental delay, and problems with vision.Behavioral and psychiatric problems can be present and most commonly include attention deficit hyperactivity disorder, autistic features, and sleep disturbances. While most individuals with a 1q21.1 deletion look like their other family members, some common facial features include prominent forehead (which contributes to a more overall triangular head-shape), deep-set eyes, and a somewhat rounded nose.
Although most children diagnosed with 1q21.1 deletions do not have major clinical symptoms, a few children among this population have been reported to have congenital heart disease, kidney and urinary tract problems, poor bone health, and, in some cases, seizures.
Although not always easily noticeable, features common among children with the 1q21.1 duplication include: larger-than-average head-size (known as macrocephaly), behavioral problems, somewhat distinct facial features (including more widely spaced eyes and a more prominent forehead), and irregularities of the heart. Developmental delay and intellectual impairment are common, but are not experienced by all children with this duplication. While the range of intellectual disability varies among individuals and can be anywhere from mild or moderate, many children have problems with speech and language development. While most carriers of this duplication can be affectionate and sociable, some children have been noted to display autistic-like behaviors and are diagnosed with autism spectrum disorder (also known as ASD). Less common, anxiety and attention deficit hyperactivity disorder can also be present.
The heart irregularities which have been reported in some children include: a defect in a wall of the heart (known as ventricular septal defect or univentricular heart), rearrangement of heart blood vessels (known as transposition of the great vessels or TGA), blockage of blood flow to the right side of the heart (known as pulmonary stenosis), and a group of distinct heart defects known as tetralogy of Fallot (or TOF).
Among the more rare conditions associated with the 1q21.1 duplication, seizures, spinal curvature, vision defects, and minor genital abnormalities have been reported.
Developmental delay and intellectual disability ranging from moderate to severe are common among children with a 2p15p16.1 deletion. Most have moderate to severe speech and language delay. Many children have behavioral problems including poor social interaction, repetitive behaviors, impulsiveness, inattention and hyperactivity. Some children have been diagnosed with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD).
Common facial features noted among this group of children include smaller-than-average head-size (known as microcephaly), a high forehead, a broad nasal bridge, a bulging lower lip, as well as small, widely-separated and/or downward-slanted eye openings. Drooping or hooded eyelids (a condition known as ptosis) have also been reported frequently.
Less common problems in children with the 2p15p16.1 deletion include: a high arched palate that leads to feeding difficulties, heart irregularities (including an incorrect connection between two parts of a heart valve known as bicuspid aortic valve, a blockage of blood flow to the right side of the heart known aspulmonary stenosis, and a defect in the wall of the heart known as ventricular septal defect). Genital/urinary (or genitourinary) problems include an incorrect formation of the kidney known as multicystic dysplastic kidney or MCDK, an excess of water in the kidney known as hydronephrosis, and undescended/underdeveloped testes. Problems with the feet that may occur include malformation of the middle part of the foot (known as metatarsus adductus) and a more flat and tight Achilles tendon.
Mild to severe developmental delay is common in children who test positive for a 2q33.1 deletion. While intellectual disabilities vary, many children experience learning difficulties in a moderate to severe range, the more severe of which are non-verbal. Some children will present with behavioral problems like hyperactivity, restlessness, tantrums, aggression, anxiety, sleep difficulties, and poor social interaction.
Individuals with 2q33.1 deletion have a distinctive appearance characterized by thin and sparse hair, a longer-than-average face with a small lower jaw, a high forehead, and a small mouth. Teeth and ears also have distinctive appearances while a prominent nose and downward slanting eyes are also common. Other common physical features may include smaller-than-average hands with long and thin fingers, short thumbs, and the smallest (“pinky”) finger curving inward.
Many of these children experience delays in motor development due to poor muscle tone (known as hypotonia). Additionally, most babies have feeding difficulties early on due to poor control over the muscles in the mouth and irregularities in the formation of the palate (often cleft and/or higher-than-average). Some babies have also experienced reflux. Less common problems include genital irregularities like a displaced urethra in males, a condition known as hypospadias, and undescended testicles. Also among the less common issues experienced by individuals with a 2q33.1 deletion are hernias, seizures, slow growth (both before and after birth), and irregularities of the eyes like misalignment, a condition known as strabismus, and holes in structures of the eye, a condition known as coloboma.
Features noted in children carrying a 2q37 deletion include developmental delay with mild to moderate intellectual disability. While most children in this group do learn to talk, speech tends to develop late and most of these individuals experience mild to moderate speech impairment. Behavioral problems are also common, affecting around one third of 2q37 deletion carriers.
Poor muscle tone (known as hypotonia) is common among this population of children and results in feeding problems as well as difficulty learning to crawl, walk, and grasp items. Feeding is also complicated by an increased frequency of gastro-esophageal reflux. While birth weights of these individuals tend to be normal, after birth, slow growth, short stature, and obesity are common in individuals affected by a 2q37 deletion.
Other less common conditions are hernias (especially of the umbilical and inguinal types), curving of the spine (known as scoliosis and lordosis), kidney irregularities like improper kidney positioning, urinary infections, and urinary reflux.Uncommon clinical manifestations also include congenital heart irregularities, genital irregularities in males such as small penis and undescended testicles, hearing loss, and vision problems.Despite reports of tumors in individuals with 2q37 deletion, it is unclear at this time if 2q37 deletions are associated with an increased risk of cancer.
Some common conditions associated with children testing positive for a 3q29 deletion include developmental delay and learning difficulties. Most individuals are healthy without major birth defects. The most common feature is mild speech impairment. Learning difficulties may be subtle and difficult to detect. Cognitive abilities vary between individuals with IQ scores ranging from 70 to 89 for most carriers of the deletion. About one third of this population has autistic features. Less commonly, some individuals have been diagnosed with schizophrenia and other psychological problems including aggression, anxiety, hyperactivity, and bipolar disorder with psychosis. As a result of behavioral and developmental challenges, the deletion is associated with an increased likelihood for affected individuals to experience difficulties with social skills and communication.
About half of the individuals with 3q29 deletion tend to have smaller-than-average head size (known as microcephaly). Other conditions that have been noted include the failure of a section of the heart which normally closes near the time of birth (known as ductus arteriosis) and a curving of the spine (known as scoliosis). While facial features that are common among this group of individuals may be subtle, some shared characteristics include a longer-than-average and narrower face, a shorter indent in the upper lip (which is known as the philtrum), a high nasal bridge,larger ears, and overall asymmetric facial features. Less common bodily traits include long curved fingers and a short fifth (“pinky”) finger.
Children testing positive for a 7q11.23 duplication have commonly experience developmental delays (especially in early speech and movement milestones) and varying levels of intellectual disability. Poor muscle tone (known as hypotonia) is experienced by most individuals with a 7q11.23 duplication and contributes to developmental delays. While speech and language delays are present in nearly all children of this population, the severity of these delays and the ability to overcome them varies among individuals. Intellectual ability varies among individuals, however most children experience difficulties. Behavioral problems are also common and vary in severity between individuals, with autistic tendencies and ADHD reported in more than half of children with the duplication.
Some common facial features that have been noted among this group include distinctly straight eyebrows, a higher and broader nose, deep-set eyes, a shorter indent in the upper lip (which is known as the philtrum), a thinner upper lip, and a more prominent forehead. Cleft lip or palate or both have been seen in a few cases.
Other health concerns associated with individuals with this duplication include seizures (in about one quarter of the population), which are experienced by than 25 percent have seizures. Around 20% of people with 7q11.23 duplication can have congenital heart problems.
Other less commonly encountered conditions health concerns include defects in vision and/or focusing, an outward angling of the forearm (known as cubitus valgus), misalignment of the hip joint (known as hip dysplasia), inwardly angled feet (known as talipes), and an abnormal head/neck positioning known as torticollis.
While few individuals have been diagnosed with 12q14 deletion, some common features noted in children with this deletion include stature, bone, and heart irregularities, feeding problems, intellectual disability, and developmental delay.
The feeding problems that occur in individuals with 12q14 deletion are a result of poor muscle tone (known as hypotonia) that causes difficulties with sucking, swallowing,and gastro esophageal reflux, which can cause vomiting and aspiration. Physical features seen include a prominent forehead, widely spaced eyes, deep-set eyes, long eyelashes and thin lips. Most individual with 12q14 deletion have delay in speech and language with mild to moderate impairment. Motor milestones are affected with delays in learning on crawl, walk, grab and hold things. Some individuals with deletion have intellectual disability with mild to moderate impairment.
Most individuals with 12q14 deletion do not have behavioral or mental health problems, but some have been noted to have hyperactive behavior, attention deficit hyperactivity disorder, autistic features, aggression, and autism spectrum disorder.
Other less common clinical manifestations include late dental eruption, teeth missing, curved little fingers, laxity joints, large thumbs, broad hands, puffy feet, broad toes, flat feet and a rare bone disorder where the bones have small areas of denser than normal bone. Uncommon clinical manifestations are congenital heart anomalies,eye anomalies, and kidney disease.
Some common features noted in children with a 15q24 deletion include developmental delay, intellectual disability, distinct facial and physical features, low muscle tone (which is known as hypotonia), and less-than-normal growth.
While developmental delays impact most of these individuals, there is a wide range of how severe the delays can be. Speech and learning abilities are generally severewith those more severely affected being completely non-verbal.Intellectual functioning varies between individuals from mild to severe. Delays in movement (known as motordelays) are common because ofthe hypotonia associated with this deletion.
Most individuals with the 15q24 deletion have distinct facial features such as a prominent forehead, high hairline at the front of the head, deep-set eyes,folds of skin over the inside corners of the eyes (known as epicanthal folds), aprominent nasal bridge, a very small lower jaw (known as micrognathia), a more pointed chin, and a triangular shaped face. Other commonly reported physical features includeshort fingers, shorter bones in the palms of the hands (bones known as the metacarpals),shorter-than-average thumbs,bent little fingers (pinky), incomplete development of the smallest toes, and toes which are fused together (a condition known as syndactyly).
Recurrent infections have been frequently noted in this group of individuals.Also very common among these individuals are eye abnormalities, affecting about half of this population – misalignment of the eyes (known as strabismus) is the most common. In males, common genital irregularities include a low placed urethra (which is known as hypospadias) and smaller-than-average penis size, while female genital irregularities include abnormal fusion of structures (known as labial adhesions).
Psychiatric abnormalities can be present. The most common are attention deficit hyperactivity disorder (ADHD) and aggression. Autistic features and autism spectrum disorders are less common.
Less frequently occurring concerns include hearing loss, hernias, seizures, congenital heart defects, a narrow or missing portion of the intestine (known as intestinal atresia), and an improperly formed rectum (known as imperforate anus or anorectal malformation). Despite reports of tumor in individuals with 15q24deletion, it is unclear if there is an association between this deletion and tumor growth.
Some common features reported in individuals with a 15q13.3 deletion include intellectual disability, developmental delay, seizures and behavioral difficulties. Intellectual abilities vary from mild to moderate delay, with IQ scores ranging between about 50 and 70. Speech and language delays are commonly experienced, with difficulties in forming words (known as expressive language) usually being more severe than difficulties in understanding words (known as receptive language). Many individuals with 15q13.3 deletion have poor muscle tone (known as hypotonia). This low muscle tone causes difficulty walking, further contributing to developmental delays.
Individuals with a 15q13.3 deletion do not tend to have distinct facial features that are common among this population; however, some common features have been infrequently reported. These features include wide, deep-set, or up slanting eyes, folds of skin over the inside corners of the eyes (known as epicanthal folds), a prominent groove on the upper lip (a structure known as the philtrum), and fuller-than-average lips.
Behavioral and mental health concerns commonly include autistic spectrum disorder (ASD), attention deficit hyperactive disorder (ADHD), mood disorder, impulsive behavior, and aggression. While some individuals with a 15q13.3 deletion may experience seizures, the types of seizures vary, and most individuals respond well to treatment.
Features noted in children with a 16p11.2 deletion include intellectual disability, developmental delay and autism spectrum disorder (ASD). The range of intellectual functioning varies from mild intellectual disability to normal. Verbal abilities tend to be poorer than non-verbal abilities, resulting in a majority of carriers of this deletion to require speech therapy. Difficulties in forming words (known as expressive language) are usually more severe than difficulties in understanding words (known as receptive language). Early in life, some delays in reaching movement milestones may be due to the poor muscle tone (known as hypotonia) experienced by some of these individuals.It has been estimated that obesity is present in about half of 16p11.2 deletion carriers by the age of 7.
A very large majority of individuals with the 16p11.2 deletion exhibit psychiatric conditions including autistic features – about 15% of this group are diagnosed with autism spectrum disorder (ASD).Less frequently reported psychiatric conditions include schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD), and anxiety. Seizures are present in about 1 in 4 individuals from this population.
While distinct facial features are not commonly reported, in some cases the following traits have been reported: larger-than-average head-size (known as macrocephaly), a smaller jaw (known as micrognathia), more widely-spaced eyes, a broader-than-average forehead, and flatter-than-average cheek bones and nasal bridge (the section of the face known as the mid-face).
Common concerns that have been reported in individuals with a 16p11.2 duplication include developmental delay, intellectual disability, behavioral difficulties, and psychiatric conditions. While developmental delays are very common among this group, not all children are affected. Speech and language development are commonly delayed. Early in life, movement delays (or motor delays) are the result of poor muscle tone (known as hypotonia) and loose bone-to-bone connections (known as ligamentous laxity or lax joints). As a result, milestones like sitting up, crawling, and walking are delayed. Throughout development, these individuals, on average, tend to be underweight. The spectrum of intellectual functioning varies considerably, ranging from mild-moderate intellectual disability (IQ scores of about 50) to slightly higher-than-average IQ scores of about 110.
While facial and physical features are not distinct among carriers of the 16p11.2 duplication, a smaller-than-average head-size (known as microcephaly) has been reported in some of these individuals. Other less frequently occurring features may include an outward forehead (a condition known as frontal bossing) with a higher-than-average hairline, flatter-than-average ridges above the eyes (known as hypoplastic supraorbital ridges), sparse eyebrows and eyelashes, deep-set eyes, less of an indentation in the upper lip (the structure known as the philtrum), a thin upper lip, and an overall flatter-than-average facial profile.
There is a strong association between presence of a 16p11.2 duplication and mental and behavioral health conditions. Commonly, children are overactive and have attention deficit. Frequently, this duplication is associated with an autism spectrum disorder (ASD) diagnosis. Other mental health problems are anxiety, depression, bipolar disorder and schizophrenia.
Features commonly noted in children with a 17q12 duplication include intellectual disability and developmental delay. While mild to moderate developmental delay can be present, learning (or cognitive) ability varies from mild to severe impairment. Behavioral problems can be present and can include aggression and self-injurious behaviors. Although this group of individuals tend to be quite healthy throughout life, other features that have been less frequently reported include poor muscle tone (known as hypotonia), kidney (or renal) abnormalities, and seizures varying in types in severity.
While facial features are not distinct, some common traits have been reported. These include up-slanting eyes, skin folds over the inside corner of the eyes (known as epicanthal folds), thick eyebrows with an abundance of hair between brows, and a thin upper lip.
Features that have been commonly noted in children with a 17q12 deletion include diabetes, cystic renal disease, genital tract abnormalities, developmental delays, distinctive facial features, mental health conditions, and seizures.
Developmental delay and intellectual impairment are very common. Speech and language development are frequently affected; however, despite possible early delays, many children learn to talk and develop without problems. Some subjects have movement (or motor) developmental delay, especially in tasks that require precise movements (called fine motor skills). The range of motor impairment varies greatly. The range of intellectual functioning also varies from mild to moderate delay – with IQ scores ranging between about 50 and 85.
While not every child is affected in terms of social skills, several have been diagnosed with autism spectrum disorder (ASD), autistic tendencies, or Asperger syndrome. Psychiatric problems are infrequent but can include anxiety, schizophrenia, depression, and bipolar disorder.
A large portion of individuals with 17q12 deletion have urinary tract irregularities including kidney (or renal) conditions which may be prenatally diagnosed. Additional potential abnormalities include abnormal growths in the kidney (known as cystic kidney disease or CKD), missing kidney (known as renal agenesis), and hardening of the urethra (known as urethral stenosis). While these conditions occur at a high rate in this group of individuals, most carriers of this deletion do maintain renal function without severe impairments.
Irregularities of the genital and reproductive systems are commonly present in females and males. The most common condition found in women is a developmental defect in which the uterus, cervix, and upper vagina are underdeveloped or missing. In many cases, this is not noted until reproductive age. In male subjects, genital and reproductive tract irregularities include a condition in which the scrotum surrounds the penis (known as shawl scrotum) and a low-positioned urethra (known as hypospadias).
There is a strong association between the 17q12 deletion and the development of a certain type of early onset diabetes called MODY5 (maturity onset diabetes of the young type 5). Other less common features are restricted growth, spinal curve, increased susceptibility to infections, and vision problems.
Features noted in children with a 22q11.2 duplication include developmental delay, intellectual disability, congenital heart malformation, distinct facial features, behavioral difficulties, and psychiatric concerns. The developmental delay in individuals can range from mild to moderate with speech and language being the most delayed. Movement (or motor) impairment is frequently present, especially when there is poor muscle tone (known as hypotonia). Behavior and mental health problems, with the most common being attention deficit hyperactivity disorder (ADHD) and temper control. A few individuals have been diagnosed with autism spectrum disorder (ASD) and autistic features.
Common congenital heart problems include a narrowing of the aorta known as coarctation of the aorta, in incorrectly formed channel called a patent foramen ovale (PFO), failure of a section of the heart which normally closes near the time of birth (known as ductus arteriosis), a blockage of blood flow to the right side of the heart known aspulmonary stenosis, a defect in the wall of the heart known as atrial or ventricular septal defect), and a group of distinct heart defects known as tetralogy of Fallot (or TOF).
Among the most common physical features are a broader space between the eyes, a broad flat nose, a very small lower jaw (known as micrognathia), dysplastic ears, and folds of skin over the inside corners of the eyes (known as epicanthal folds).
A significant number have some hearing loss. The common cause is a build-up of fluid inside the ear spaces that lead to temporary hearing loss. Fortunately permanent hearing loss is less common, but can occur.
An abnormality in transmitting sound and air through the oral and nasal cavity (a condition known as velopharyngeal inadequacy or VPI) is additionally very common.
Some less frequently occurring features include small kidney, a condition where the bladder extends outside of the body known as bladder exstrophy, respiratory infections, genitourinary malformations.
Features commonly noted in children with a 22q11.2 distal deletion include congenital heart disease, distinct facial features, irregularities in the formation of the roof of the mouth (the palate), abnormalities in transmitting sound and air through the oral and nasal cavity (a condition known as velopharyngeal inadequacy or VPI), and learning difficulties.
Congenital heart disease is the most frequent finding in 22q11.2 deletion. Individuals with the deletion may have learning difficulties with a mild to average IQ scores. Developmental delay is frequently seen with speech.
Some individuals may have distinct facial features such as more arched eyebrows, deeper-set eyes, smoother indent in the upper lip (known as the philtrum), thin upper lip, a distinctive nose (a condition known as hypoplastic alae nasi), and a small, pointed chin. These traits vary and can be undetected, subtle, or mild.
Other less common clinical features include immune deficiency leading to frequent infections, low calcium levels (known as hypocalcemia), psychiatric illness, kidney (or renal) irregularities, hearing loss, growth hormone deficiency, seizures, and skeletal abnormalities.
Some common features noted in children with a 22q11.2 deletion include congenital heart disease, immune deficiency, low calcium levels (known as hypocalcemia), abnormalities in the formation of the roof of the mouth (known as the palate), learning difficulties, and distinct facial features.
Developmental delay is common although not universal. Movement (or motor) milestones are commonly affected with difficulties in feeding and delays in learning to crawl, walk, grab and hold things due to low muscle tone (known as hypotonia). While many individuals with a 22q11.2 deletion learn to speak well, speech and language development can be affected. Difficulties in forming words (known as expressive language) are usually more severe than difficulties in understanding words (known as receptive language). Intellectual disabilities range from mild to moderate.
Poor social skills are common as individuals with 22q11.2 deletion are often impulsive, shy, and suffer from mood swings. While a high rate of mental health conditions are associated with this deletion, not every child is affected. The most common diagnoses are autism spectrum disorder (ASD), autistic features, and attention deficit hyperactivity disorder (ADHD).
22q11.2 deletion is known as the second most common genetic cause of congenital heart defects after Down’s syndrome. Common congenital heart problems include a narrowing of the aorta known as coarctation of the aorta, in incorrectly formed channel called a patent foramen ovale (PFO), failure of a section of the heart which normally closes near the time of birth (known as ductus arteriosis), a blockage of blood flow to the right side of the heart known aspulmonary stenosis, a defect in the wall of the heart known as atrial or ventricular septal defect), and a group of distinct heart defects known as tetralogy of Fallot (or TOF).
Autoimmune disorders like idiopathic thrombocytopenia purpura and polyarticular juvenile rheumatoid arthritis are frequently associated with 22q11.2 deletion syndrome. Calcium levels are commonly low (a condition known as hypocalcemia) and can manifest as jitteriness, seizures, muscle cramps, and tingling of the mouth and fingers. The calcium levels usually become normal through development, although some individuals experience recurrence. Some people with 22q11.2 deletion can have seizures. The possible cause is the low calcium levels (hypocalcemia), but in most of cases, the seizures are a result of improper brain activity. The types of seizures vary and in most cases respond to treatment.
Some individuals with 22q11.2 deletion present distinct facial and body features, such as broadly spread eyes, a dimple where the ear connects to the head known as a preauricular sinus, outwardly extended ears, prominent tip of the nose, a distinctive nose (a condition known as hypoplastic alae nasi), cleft lip and palate, longer-than-average face, flatter feet, smaller chin and mouth (known as micrognathia), and a skull abnormality known as craniosynostosis).