17q12 microdeletion syndrome

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17q12 microdeletion syndrome
Other names17q12 deletion syndrome
neuroatypicality
Usual onsetConception
DurationLifelong
CausesChromosome microdeletion
Diagnostic methodFluorescence in situ hybridization

17q12 microdeletion syndrome, also known as 17q12 deletion syndrome, is a rare

autism and schizophrenia
.

17q12 microdeletion syndrome is not to be confused with 17q12 microduplication syndrome, caused by the addition of genetic material in the same region from which it is removed in the microdeletion, or 17q21.31 microdeletion syndrome, another name for Koolen–De Vries syndrome.

Presentation

17q12 microdeletions have a variable phenotype, ranging from few or no symptoms to severe disability. The condition is thought to be underdiagnosed, and cases with milder phenotypes may not reach clinical attention unless they have an affected child themselves.[1][2] The most characteristic symptom is renal cysts and diabetes syndrome (RCAD), also known as "type 5 diabetes", which is caused by deletion of the associated HNF1B gene in the region.[3] RCAD is associated with kidney abnormalities and a characteristic form of diabetes that causes atrophy of the pancreas. However, some people with 17q12 microdeletions have normal renal function.[2] RCAD is diagnosed in approximately 40% of people with 17q12 microdeletions, usually prior to age 25, while kidney abnormalities more broadly occur in approximately 85-90%.[4]

People with 17q12 microdeletions have a characteristic facial phenotype, albeit a subtle one not usually obvious in daily life.

epicanthic folds.[4] Pathological short stature is possible, and a characteristic "short and stocky" body shape occurs in many cases.[1]

17q12 microdeletions are associated with neurocognitive and developmental involvement of variable severity. Some have mild to moderate

autism spectrum disorder, with significant increases in both diagnosis and subclinical autistic traits.[7][8] 17q12 microdeletions have been implicated as one of the major genetic causes of high-functioning autistic spectrum disorders.[1] Schizophrenia is also a significant psychiatric complication of 17q12 microdeletion syndrome. 17q12 microdeletions are estimated to occur in approximately 1 in 1,600 people with schizophrenia, compared to an estimation of below 1 in 50,000 in the general population.[8] Epilepsy, usually mild, occurs in approximately one-third of cases.[6]

Reproductive system anomalies are associated with 17q12 microdeletions, particularly in females. 17q12 microdeletions have been linked to uterine malformations, most frequently

vaginal canal are absent.[4][9]

Autosomal dominant inheritance

Causes

17q12 microdeletion syndrome is an

autosomal dominant disorder, where one copy of the relevant mutation is enough to cause the condition. Most cases are de novo, or spontaneous mutations that do not occur in the proband's parents;[10] approximately 75% are de novo, while 25% are inherited.[4] People with 17q12 microdeletions who have normal fertility have a 50% chance of passing the deletion down to their offspring.[1] Environmental factors have not been implicated in the syndrome.[1]

Diagnosis

Like other chromosomal microdeletions, 17q12 microdeletion syndrome is diagnosed via

karyotyping, used to diagnose major chromosomal disorders such as aneuploidy, is rarely sensitive enough to detect microdeletions.[11]

Treatment

As the underlying 17q12 microdeletion is an innate genetic disorder, it cannot by itself be treated. Rather, treatment is symptomatic and supportive. The high prevalence of kidney disease indicates routine monitoring of renal function, particularly in people taking potentially nephrotoxic medications such as

neuroleptic drugs in those with a mental health diagnosis.[4]

Epidemiology

The prevalence of 17q12 microdeletion syndrome is unknown, and it is likely to be underdiagnosed. 17q12 microdeletions are estimated to occur in approximately 1 in 600 people on the autism spectrum and 1 in 1,600 with schizophrenia, but are far rarer in the general population.[8] General prevalence is estimated to be between 1 in 14,000[4] and 1 in 62,500.[12]

In addition to the increased prevalence in autism and schizophrenia, some other clinical populations have increased prevalence of 17q12 microdeletion syndrome. The condition occurs in approximately 2% of those with congenital kidney abnormalities and 3-6% of women with Müllerian agenesis.[4] It is one of the ten most common microdeletions amongst children with idiopathic developmental delay.[1]

Microduplication

17q12 microduplication syndrome is far rarer than the corresponding microdeletion, estimated to occur roughly one-fifth as frequently as 17q12 microdeletion syndrome. Due to its rarity and the overlap between their phenotypes, 17q12 microduplications are usually discussed as an adjunct to microdeletions.[3] Like the microdeletion syndrome, the microduplication syndrome has a broad phenotypic range, ranging from asymptomatic to profound disability; intellectual disability is frequently but not always more severe than the microdeletion, while physical health is often better.[13][14] Epilepsy is a frequent finding. A case of sex reversal has been reported.[13] While autism comorbid with 17q12 microduplication has been reported, it appears far rarer than in the microdeletion.[15] Physical anomalies associated with 17q12 microduplication syndrome include syndactyly, microcephaly, epicanthic folds, and thick eyebrows or a unibrow.[13][14] The 17q12 microduplication appears to have a low penetrance, as many cases are inherited from asymptomatic parents.[13]

See also

References

  1. ^ a b c d e f Unique, Moreno de Luca D, Hultén M (2018). "17q12 microdeletions" (PDF). Unique.
  2. ^
    PMID 22511894
    .
  3. ^
    PMID 31131025
    .
  4. ^
    PMID 27929632
    .
  5. PMID 19844256
    .
  6. ^
    PMID 17924346
    .
  7. ^
    PMID 27234567
    .
  8. ^
    PMID 21055719
    .
  9. PMID 19889212
    .
  10. ^ Genetics Home Reference. "What is a gene mutation and how do mutations occur?". Medline Plus. Retrieved 22 February 2021.
  11. ^
    S2CID 20989937
    .
  12. PMID 30032214
    .
  13. ^
    S2CID 12242509
    .
  14. ^ a b Unique, Girisha KM (2018). "17q12 microduplications" (PDF). Unique.
  15. S2CID 20832319
    .

External links

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