Classical microdeletion

Clinical description

The classical microdeletion of the 16p11.2 region was brought out for the first time in 2008 as a recurrent microdeletion in individuals affected by autism spectrum disorders.

Associated malformations

  • Developmental delay
  • The majority of individuals carrying a deletion of this region present, to a varying degree, a developmental delay. Diagnostic of this condition is often made following investigations made in the context of a developmental delay, intellectual disability or an autism spectrum disorder. Besides, language and cognitive functions seem to be most affected in these individuals whereas motors functions are less affected.

  • Cognitive troubles
  • Carriers of this microdeletion have an IQ score that is on average 30 points lower than their relatives’ who do not carry the deletion. Those cognitive results are in favor of an inconstant intellectual disability, which varies from moderate to normal, although the majority of cases presents learning disabilities.

  • Speech delay
  • Language acquisition is delayed in children who carry a 16p11.2 deletion. In general, expressive language is more problematic than receptive language. 80% of children who carry a 16p11.2 microdeletion will require speech therapy.

  • Neurological troubles
  • Seizures happen in 18% of cases. Some children have been reported having movement disorder especially dystonia, which is characterised by involuntary muscle contractions.

  • Psychiatric troubles
  • Autism: 15% of children who carry the proximal microdeletion in 16p11.2 region meet the diagnostic criteria of autism spectrum disorder.

    In 80% of cases, children present an associated psychiatric trouble (ADDH, behavioural trouble, anxiety, etc).

  • Predisposition to overweight and obesity
  • The associated risk of obesity is of 50% at 7 years old. 70% of adult carriers present a body mass index over 85e percentile. 45% of them present a severe morbidly obese state.

  • Malformations
    • Some abnormalities have been reported more frequently in carriers of the 16p11.2 deletion. Especially, vertebral and craniocervical abnormalities have been observed. Among these include hemivertebrae, vertebral fusion and platybasia.
    • Chiari malformation has also been identified on MRI of some carriers. Rarely, a syringomyelia can be present.
    • Cardiac malformations have been reported in 5% of cases.
  • Size
  • Adult carriers are smaller than average (-1 standard deviation).

    Medical recommandations

    To take account of the range of possible symptoms in carrier subjects, the following are recommended (and to adapt case per case):

    • Routine clinical exam including a weight surveillance and an exam of all organs;
    • Follow-up of the child’s development (cognitive and behavioural tests);
    • Consider neurology consultation and an EEG test whether the probability of seizures is high;
    • In patients with a spinal curvature, radiographs of the spine are recommended;
    • Consultation with a cardiologist in some cases necessary (echocardiogram);
    • Assessment of blood pressure and blood sugar in overweight or obese patients.

    Treatment of manifestations

    • Contact medical specialists to the specific signs ( neurologist , geneticist, pediatrician specialists development / behavioral disorders). It is also strongly recommended to contact a neuropsychologist to provide a comprehensive cognitive profile for the purpose of an accurate diagnosis and appropriate treatment.
    • Monitoring the development of the child is recommended because of the high rate of occurrence of language disorders, intellectual disabilities and the appearance of autism spectrum disorders.
    • The American Academy of Pediatrics has established guidelines for the monitoring and screening to identify patients with autism spectrum disorders [Johnson et al 2007] and recommendations for the management of children with disorders of the autism spectrum [Myers et al 2007]. See Miller et al, 2011
    • Neurology consultation to prevent the occurrence of seizure disorders.
    • Nutritional counseling and weight monitoring (proactive prevention of obesity).

    Heredity

    • Transmission: Microdeletions are transmitted on an autosomique dominant mode. A carrier has a 50% probability to transmit this deletion to his descent.
    • In 30% of cases, 16p11.2 microdeletion is inherited from a parent. The risk for the brothers and sisters to also inherit this deletion is of 50%. The rest of the time, the microdeletion has happened de novo, at conception of the affected person. The risk for her brothers and sisters is therefore similar to the general population.
    • Prenatal diagnosis: Prenatal diagnosis is technically feasible by a chorionic villus sampling from 11 weeks of pregnancy or by an amniocenthesis from 15 weeks of pregnancy. Little requests have been done for this condition because of the clinical variability and the impossibility to predict the manifestations.

    Duplication

    Carriers of the duplication (three copies of the region instead of 2) have a mirror clinical presentation. Indeed, they present a high risk of underweight, microcephaly, and schizophrenia (Jacquemont 2011; Shinawi, 2010).

    Notes that little is know about the disease and this is why it's very important for studies to understand how this region can cause difficulties for some individuals carrying a certain rearrangement, and save others with the opposite one.

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