16p11.2 deletion syndrome is a rare genetic condition caused by microdeletion on the short arm of chromosome 16. Most affected individuals experience

global developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive development, cognitive and developmental biology, physical development. It can be diagnosed when a child is delayed in one or more milest ...

and intellectual disability, as well as childhood-onset

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

. 16p11.2 deletion is estimated to account for approximately 1% of autism spectrum disorder cases.

Signs and symptoms

Developmental and behavioral

The most commonly observed features of 16p11.2 deletion syndrome are

and psychiatric or behavioral issues, though severity varies significantly. Most people with the deletion don't have intellectual disability, but many have learning disabilities. The average IQ of individuals with 16p11.2 deletion syndrome is approximately 2 standard deviations below that of family members without the deletion. Many have language disorders and

motor speech disorders Motor speech disorders are a class of speech disorders that disturb the body's natural ability to speech, speak due to neurologic impairments. These neurologic impairments make it difficult for individuals with motor speech disorders to plan, prog ...

including

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...

and apraxia. Half of affected individuals have at least one psychiatric or behavioral diagnosis. Approximately 30% of individuals are diagnosed with

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

. Approximately 20-25% of individuals are diagnosed with

autism spectrum The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

disorder (ASD), and nearly all share some behavioral traits with ASD.

Neurologic

Up to 25% of affected individuals experience

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s. The most common type is tonic-clonic seizure; complex

focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...

s and

absence seizure Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized by ...

s are also reported. Many individuals may exhibit

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

, CT, or MRI abnormalities. Hyporeflexia,

gait abnormalities Gait is the pattern of movement of the limbs of animals, including humans, during locomotion over a solid substrate. Most animals use a variety of gaits, selecting gait based on speed, terrain, the need to maneuver, and energetic efficiency. Di ...

, and truncal or symmetric limb

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...

were observed in at least 15% of individuals in a cohort of 136 16p11.2 deletion carriers.

Sensorineural Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve ( cranial nerve VIII). SNHL accounts for about 90% of r ...

or conductive hearing loss and paroxysmal kinesigenic choreoathetosis are observed in some individuals.

Obesity

16p11.2 deletion syndrome strongly predisposes individuals to increased

body mass index Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...

(BMI) and

beginning in childhood. BMI in individuals with the syndrome is significantly higher than that in the general population by age 5, and 50% of carriers are obese by age 7. By adulthood, 75% of individuals are obese. Affected individuals report hyperphagia due to sensory and social cues or boredom. Obesity and related comorbidities such as

insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

comprise the majority of medical challenges for adults with 16p11.2 deletion syndrome.

Other

Macrocephaly is slightly more prevalent in 16p11.2 deletion syndrome compared to the general population. Approximately one-third of individuals have a sacral dimple or

café au lait spot ''Café au lait'' spots, or ''café au lait'' macules, are flat, hyperpigmented birthmarks. The name ''café au lait'' is French for "coffee with milk" and refers to their light-brown color. Café au lait lesions with rough borders (" coast of Mai ...

s. Vertebral anomalies associated with scoliosis are also observed. 16p11.2 deletion has been associated with a 13.9-fold increased risk of

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...

Genetics

16p11.2 deletion syndrome is caused by a

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

microdeletion In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...

of ~600 kilobases between the recurrent breakpoint regions BP4 and BP5 on the

short arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or ...

of chromosome 16. Genes in the BP4-BP5 region include the following: * SLC7A5P1 *

SPN SPN may refer to: Places * Saipan International Airport (IATA airport code: SPN), Saipan * Shahjahanpur railway station (station code: SPN), Uttar Pradesh, India * Spooner Row railway station (National Rail station code: SPN), South Norfolk, Engla ...

* QPRT * C16orf54 * ZG16 *

MAZ Maz or MAZ may refer to: * IATA code for Eugenio María de Hostos Airport, Mayagüez, Puerto Rico * Minsk Automobile Plant, abbreviated in Belarusian as MAZ * Myc-associated zinc finger protein, a protein encoded by the ''MAZ'' gene * Maz, a villa ...

* PRRT2 * C16orf53 * MVP * CDIPT * SEZ6L2 * ASPHD1 * KCTD13 *

TMEM219 Transmembrane protein 219 also known as insulin-like growth factor-binding protein 3 receptor or IGFBP-3R is a protein that in humans is encoded by the TMEM219 gene. IGFBP-3R acts as a cell death receptor for IGFBP3 Insulin-like growth factor-bi ...

TAOK2 Serine/threonine-protein kinase TAO2 is an enzyme that in humans is encoded by the ''TAOK2'' gene. Interactions TAOK2 has been shown to interact with MAP2K6 and MAP2K3 Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme ...

* HIRIP3 * INO80E *

DOC2A Double C2-like domain-containing protein alpha is a protein that in humans is encoded by the ''DOC2A'' gene. There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domai ...

* C16orf92 * FAM57B *

ALDOA Aldolase A (ALDOA, or ALDA), also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ''ALDOA'' gene on chromosome 16. The protein encoded by this gene is a glycolytic enzyme that catalyzes the reversible conve ...

PPP4C Serine/threonine-protein phosphatase 4 catalytic subunit is an enzyme that in humans is encoded by the ''PPP4C'' gene. Interactions PPP4C has been shown to interact with: * CCDC6, * CCT2, * CCT3, * CCT4, * CCT5, * CCT6A, * CCT7, * IG ...

TBX6 T-box 6 is a protein that in humans is encoded by the TBX6 gene. Function This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involv ...

YPEL3 Yippee-like 3 (Drosophila) is a protein that in humans is encoded by the YPEL3 gene. YPEL3 has growth inhibitory effects in normal and tumor cell lines. One of five family members (YPEL1-5), YPEL3 was named in reference to its Drosophila melanogas ...

* GDPD3 * MAPK3 * CORO1A * BOLA2 * SLX1A * SLX1B *

SULT1A3 Sulfotransferase 1A3/1A4 is an enzyme that in humans is encoded by the ''SULT1A3'' gene. Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are ...

* SULT1A4 Nearby regions on chromosome 16 may also be affected. Notably, deletion of ''

SH2B1 SH2B adapter protein 1 is a protein that in humans is encoded by the ''SH2B1'' gene. Interactions SH2B1 has been shown to interact with: * Grb2, * Insulin receptor, * Janus kinase 2, and * TrkA. Clinical significance Variations close to ...

'' is associated with obesity and may be involved in the pathogenesis of obesity observed in the syndrome. 16p11.2 deletion typically occurs by

de novo mutation A de novo mutation is any mutation/alteration in the genome of any organism (humans, animals, plant, microbes, etc.) that wasn't present or transmitted by their parents. This type of mutation (like any other) occurs spontaneously during the process ...

. Approximately 7% of affected individuals inherit the mutation from a parent in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

fashion. Parents carrying the deletion often have no history of intellectual disability or autism spectrum disorder. Prevalence of 16p11.2 deletion syndrome was initially estimated to be 3 in 10,000 in the general population, though more recent estimates have increased to 1 in 2,000.

Management

Management of 16p11.2 deletion syndrome is highly variable and based on an individual's specific symptoms or deficits. Interventions may include

special education Special education (known as special-needs education, aided education, exceptional education, alternative provision, exceptional student education, special ed., SDC, or SPED) is the practice of educating students in a way that accommodates th ...

, psychiatric treatment, standard

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

treatment, audiology assessment,

physical Physical may refer to: *Physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally co ...

and

occupational therapy Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...

for gross/fine motor skills, and regular monitoring of congenital anomalies or defects. Due to increased risk of obesity associated with the syndrome, psychiatric medications associated with weight gain are not recommended. Social work involvement and community support can also benefit affected individuals and caregivers.

References

External links

{{Medical resources , DiseasesDB = , ICD11 = LD44.G1 , ICD10 = Q93.5 , ICD9 = , ICDO = , OMIM = 611913 , GARDNum = 10740 , GARDName = Proximal 16p11.2 microdeletion syndrome , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , Orphanet = 261197 Syndromes with intellectual disability Syndromes with obesity Syndromic autism Autosomal monosomies and deletions Autosomal dominant disorders