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Proximal 16p11.2 microdeletion syndrome

MedGen UID:
461504
Concept ID:
C3150154
Disease or Syndrome
Synonyms: 16p11.2 deletion syndrome; 16p11.2 Microdeletion; Chromosome 16p11.2 deletion syndrome; CHROMOSOME 16p11.2 DELETION SYNDROME, 593-KB
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0012756
OMIM®: 611913
Orphanet: ORPHA261197

Definition

The 16p11.2 recurrent deletion phenotype is characterized by motor speech disorder, language disorder, motor coordination difficulties, psychiatric conditions, and autistic features. While most, if not all, individuals with the 16p11.2 recurrent deletion experience some degree of developmental delay, the severity varies significantly. Most affected individuals do not have intellectual disability (defined as an IQ of <70), but many have below average cognition and learning disabilities in both verbal and nonverbal domains. Obesity is a feature of this disorder and generally emerges in childhood; BMI in individuals with the 16p11.2 recurrent deletion is significantly higher than in the general population by age five years. Seizures are observed in approximately 25% of individuals with the recurrent deletion. Vertebral anomalies, hearing impairment, macrocephaly, and cardiovascular malformation have each been observed in some individuals. Clinical follow-up data from adults suggests that the greatest medical challenges are obesity and related comorbidities that can be exacerbated by medications used to treat behavioral and psychiatric problems. [from GeneReviews]

Additional description

From MedlinePlus Genetics
16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.

People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. In 16p11.2 deletion syndrome, expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Some people with this disorder have recurrent seizures (epilepsy).

Some affected individuals have minor physical abnormalities such as low-set ears or partially webbed toes (partial syndactyly). People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities.  https://medlineplus.gov/genetics/condition/16p112-deletion-syndrome

Clinical features

From HPO
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProximal 16p11.2 microdeletion syndrome

Recent clinical studies

Etiology

Giaroli G, Bass N, Strydom A, Rantell K, McQuillin A
Schizophr Res 2014 Nov;159(2-3):340-6. Epub 2014 Oct 11 doi: 10.1016/j.schres.2014.09.025. PMID: 25311781
Hempel M, Rivera Brugués N, Wagenstaller J, Lederer G, Weitensteiner A, Seidel H, Meitinger T, Strom TM
Am J Med Genet A 2009 Oct;149A(10):2106-12. doi: 10.1002/ajmg.a.33042. PMID: 19676056

Diagnosis

Lefebvre M, Duffourd Y, Jouan T, Poe C, Jean-Marçais N, Verloes A, St-Onge J, Riviere JB, Petit F, Pierquin G, Demeer B, Callier P, Thauvin-Robinet C, Faivre L, Thevenon J
Clin Genet 2017 Jun;91(6):908-912. Epub 2017 Feb 22 doi: 10.1111/cge.12918. PMID: 27861764

Prognosis

Hempel M, Rivera Brugués N, Wagenstaller J, Lederer G, Weitensteiner A, Seidel H, Meitinger T, Strom TM
Am J Med Genet A 2009 Oct;149A(10):2106-12. doi: 10.1002/ajmg.a.33042. PMID: 19676056

Clinical prediction guides

Lefebvre M, Duffourd Y, Jouan T, Poe C, Jean-Marçais N, Verloes A, St-Onge J, Riviere JB, Petit F, Pierquin G, Demeer B, Callier P, Thauvin-Robinet C, Faivre L, Thevenon J
Clin Genet 2017 Jun;91(6):908-912. Epub 2017 Feb 22 doi: 10.1111/cge.12918. PMID: 27861764
Battaglia A, Novelli A, Bernardini L, Igliozzi R, Parrini B
Am J Med Genet A 2009 Jun;149A(6):1200-4. doi: 10.1002/ajmg.a.32847. PMID: 19449418

Recent systematic reviews

Giaroli G, Bass N, Strydom A, Rantell K, McQuillin A
Schizophr Res 2014 Nov;159(2-3):340-6. Epub 2014 Oct 11 doi: 10.1016/j.schres.2014.09.025. PMID: 25311781

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