Understanding Deletion Syndromes
Empowering Families and Advancing Awareness
What Are Deletion Syndromes?
Deletion syndromes are a group of genetic disorders caused by the loss of a segment of DNA from a chromosome. There is no fixed number of deletion syndromes, as hundreds of distinct, rare chromosomal deletions exist. These deletions can vary in size and location, and their effects depend on which genes are missing and how they impact the body’s development and functioning. Many syndromes are microdeletions resulting from tiny missing pieces of DNA (up to 5Mb) that affect multiple genes. While individual syndromes are rare, collectively they are a significant cause of developmental delay and congenital anomalies. Almost any chromosome can have a deletion, with hundreds of different potentially clinically relevant, and rare deletion sites identified. Deletions can be terminal (end of a chromosome) or interstitial (interior of a chromosome).
Deletion syndromes are typically identified through genetic testing, such as chromosomal microarray or karyotyping, and can occur spontaneously or be inherited from a parent. Individuals with deletion syndromes may experience a wide range of physical, developmental, and medical challenges, and care often involves a multidisciplinary team to address their unique needs. The projected life span can vary widely, as can levels of functioning. Each person with a deletion syndrome needs to be seen as an individualized case with no assumptions made about them without knowing the details of their unique presentation. Parents of children with deletion syndromes often act as case managers for their children, whether they are minors or adults. Below you will find information on some of the more common deletion syndromes.
22q11.2 Deletion Syndrome (DiGeorge Syndrome)
The most common deletion syndrome is 22q11.2 deletion syndrome, also known as DiGeorge syndrome or velocardiofacial syndrome. It occurs in 1 in 4000 births. This condition results from a missing segment on chromosome 22. While usually a random, non-inherited event, it is a leading genetic risk factor for both autism and psychosis. Symptoms often include heart defects such as ventricular septal defects; a small or absent thymus causing low T-cell production, leading to immunodeficiency; small, low-set ears; cleft palate; hooded eyes; a long face; hypoparathyroidism leading to low calcium levels; learning disabilities; and developmental delays. These conditions can lead to severe infections due to weakened immunity, chronic feeding difficulties, severe heart failure, and seizures due to low calcium. Most individuals with this syndrome live into adulthood, with a life span extending into the fifties or beyond, but early diagnosis and intervention are crucial for managing health issues and supporting developmental milestones.
Williams Syndrome
Williams syndrome, also known as Williams–Beuren syndrome (WBS), is caused by a deletion on chromosome 7. This syndrome is not typically inherited; it usually occurs as a random, de novo event during the formation of reproductive cells. It results from a deletion of roughly 25 to 28 genes on chromosome 7q11.23, which includes the gene responsible for creating the protein elastin. The lack of elastin causes both connective tissue and vascular issues. Williams Syndrome is characterized by distinct “elfin-like” facial features: a small, upturned nose, full cheeks, a wide mouth, full lips, a small chin, and puffiness around the eyes. It also tends to include cardiovascular disease (e.g., supravalvular aortic stenosis), mild-to-moderate intellectual disability, and a highly gregarious, empathetic, and sociable personality. Developmental delays, learning disabilities, and difficulties with spatial tasks, often paired with strong verbal skills are common. People with this syndrome tend to be of short stature, have low muscle tone, experience feeding difficulties in infancy, grapple with hypercalcemia (elevated blood calcium), and deal with sensitive hearing (hyperacusis), and musculoskeletal problems. People with Williams Syndrome may have an intense interest in music, a strong social drive, some anxiety, Attention Deficit Hyperactivity Disorder (ADHD), and phobias, particularly of loud noises. Medical care for Williams syndrome focuses on monitoring heart health and supporting educational and social development.
Prader-Willi Syndrome (PWS)
.PWS is a genetic condition caused by the loss of function of specific genes on chromosome 15, usually inherited from the father (paternal chromosome). It occurs randomly, though it can also result from maternal uniparental disomy or imprinting errors. This syndrome is characterized by intellectual disabilities, a weak cry in infancy, short stature, underdeveloped sex organs, and behavioral challenges. It also tends to include insatiable hunger, which can lead to obesity if not managed. Early life features include weak muscles (floppiness), feeding difficulties with a poor suck reflex, and failure to thrive. Body characteristics include a narrow forehead, almond-shaped eyes, small hands and feet, short stature, and light skin and hair. Behaviors often include obsession with food; stubbornness; and skin picking; as well as obsessive-compulsive behaviors; severe temper outbursts; and sometimes, psychosis in young adulthood. While life-threatening complications (e.g., severe obesity, sleep apnea, respiratory issues) exist, life expectancy has improved with early diagnosis and management of nutrition and hormonal issues.
Wolf-Hirschhorn Syndrome
Wolf-Hirschhorn syndrome (WHS) is caused by a deletion on the short arm of chromosome 4. WHS is a rare genetic disorder affecting approximately 1 in 50,000 births. It is more prevalent in females than it is in males, affecting them twice as often. Common features include a distinct appearance, characterized by the “Greek warrior helmet” facial features. This includes a broad, flat nasal bridge; a high forehead; protruding eyes (hypertelorism), arched eyebrows, a small chin (micrognathia), and a downturned mouth. In addition, this syndrome comes with severe growth retardation, intellectual disability, and seizures. Children with Wolf-Hirschhorn syndrome often require ongoing medical care and early intervention services to support their development and quality of life. Treatment focuses on managing symptoms, such as epilepsy, feeding issues, and structural defects. People with WHS tend to have significant delays in motor skills and speech, slow growth before and after birth (prenatal/postnatal), resulting in short stature, small head size (microcephaly), hypotonia (weak muscle tone), cleft lip/palate, heart defects, and skin tags or pits in front of the ears.
1p36 Deletion Syndrome
This syndrome is one of the most common of these genetic differences, estimated to occur in 1 in 5,000 to 10,000 births. It is still a rare, congenital disorder caused by the loss of a small segment on the short (p) arm of the first chromosome. It is characterized by moderate-to-severe intellectual disability, developmental delays, limited speech, distinct facial features, hypotonia (weak muscle tone), and seizures. Most cases occur sporadically, though some are inherited. This syndrome tends to have characteristically deep-set eyes, straight eyebrows, midface hypoplasia, a broad/flat nose, pointed chin, and low-set, backward-rotated ears, a significant speech delay (often nonverbal or limited to a few words), severe intellectual disability, and developmental delays. People with 1p36 tend to have seizures (often difficult to treat), along with micro-brachycephaly (small head), hypotonia, congenital heart defects, skeletal anomalies (shortened fingers/toes), vision/hearing impairments, and swallowing difficulties. In addition, behavioral issues are common, including temper tantrums and self-biting, and autism or autistic-like features.
Cri-du-chat Syndrome
Cri du chat syndrome, or cat cry syndrome, is a rare genetic disorder that happens because of a missing piece (deletion) of a chromosome. This deletion most often occurs randomly during the formation of reproductive cells (eggs or sperm) in early fetal development. The parents of a child with a random deletion usually have normal chromosomes. It gets its name from the distinct cry that infants with the disease make. “Cri du chat” means “cry of the cat” in French. The most common symptom of the disorder is a distinct high-pitched, shrill cry. It may be present during the first few weeks of your baby’s life, but it becomes less noticeable as your baby grows older. 5p- (pronounced “5p minus”) syndrome is another name for the condition. 5p- describes the genetic deletion on the small arm (the p arm) of chromosome 5. 5p-syndrome is a spectrum disorder. The size and location of the deletion can vary, so symptoms can range from mild to severe. If someone has a larger deletion, they may have more serious symptoms. These can include: small head (microcephaly); widely spaced eyes (hypertelorism); a round face; significant motor and cognitive impairments, including language difficulties; feeding difficulties; constipation; and frequent infections (ear, respiratory).Cri du chat syndrome is a rare disorder, but it’s one of the most commonly seen chromosomal anomalies. The disease occurs in 1 in 15,000 to 1 in 50,000 live births in the U.S.
Miller-Dieker Syndrome
MDS is a rare, fatal genetic disorder caused by a deletion on chromosome 17, characterized by lissencephaly (a smooth brain surface). It causes severe intellectual disability, profound developmental delays, seizures, and weak muscle tone. Most children with this syndrome do not survive beyond early childhood, with most children passing away by age 2, though some may live slightly longer. These babies tend to have a prominent forehead, sunken midface, upturned nose, low-set ears, a small jaw, microcephaly (small head size), and feeding difficulties. In addition, they have slow growth, heart defects, kidney issues, and/or abdominal organ protrusion (omphalocele). Most cases are not inherited, resulting from a random deletion during the formation of reproductive cells or early embryonic development. In some cases, a parent carries a balanced rearrangement of chromosome 17, which becomes unbalanced in the child. Confirmed through genetic testing (FISH) or prenatal ultrasound, which may show a smooth brain or intrauterine growth restriction. Treatment is symptomatic and supportive, including anti-seizure medication, feeding tubes for nutrition, and therapies for physical or developmental challenges.
Smith-Magenis Syndrome
SMS is a rare, complex neurodevelopmental disorder caused by a chromosome 17p11.2 deletion (90% of cases) or RAI1 gene mutation. The condition is usually a de novo (not inherited) deletion in the 17p11.2 region. It affects approximately 1 in 15,000 to 25,000 individuals and is confirmed through genetic testing, such as a chromosomal microarray. It causes intellectual disability, speech/motor delays, and distinctive facial features such as a square-shaped face, deep-set eyes, full cheeks, a flat nasal bridge, and a downward-slanting mouth. It also includes behavioral issues, including self-injury; tantrums; impulsivity; hyperactivity; attention-seeking; and self-injurious behaviors (e.g., skin picking, head banging, biting). A hallmark symptom is severe insomnia, excessive daytime sleepiness, and waking up frequently during the night due to inverted circadian rhythms While there is no cure, symptom management is crucial. Melatonin in the evening and beta-blockers in the morning may be needed to regulate the sleep-wake cycle. Early intervention with speech, occupational, and physical therapy will assist with delays as these children have mild-to-moderate intellectual disability, speech delay, scoliosis, short stature, and ear/hearing issues. Additionally, they will need management of behavioral challenges through psychiatric care, education, and support programs.
Jacobsen Syndrome
Jacobsen syndrome is a rare genetic disorder caused by a deletion of genetic material from chromosome 11, resulting in developmental delays, cognitive impairment, distinct facial features (small/low-set ears, ptosis, wide-set eyes), and a high prevalence of congenital heart defects. 20% of infants may not survive the first year, largely due to the severe cardiac issues. Affecting roughly 1 in 100,000 births, it often includes the Paris-Trousseau bleeding disorder, as well as kidney and gastrointestinal issues. Deletion of the terminal end of the long arm (q) of chromosome 11 is usually a random event, but can be inherited. Developmental delays (speech and motor skills), cognitive impairment, ADHD-like behaviors, feeding difficulties, and recurrent infections are common with this syndrome. These children tend to have small/low-set ears, hypertelorism (wide-set eyes), ptosis (droopy eyelids), epicanthal folds, and a short nose. No cure exists; treatment is symptomatic, including specialized care for heart defects, developmental therapies, and monitoring of blood disorders.
We know that there are many, many more deletion syndromes. We learn more about the variety every day. Please drop us a line with information about your syndrome, or that of someone you love. All are welcome.