Clinical Description
To date, published reports include 86 individuals with the 17q12 recurrent duplication, along with some phenotypic data [Sharp et al 2006, Mefford et al 2007, Mencarelli et al 2008, Nagamani et al 2010, Faguer et al 2011, Brandt et al 2012, Bierhals et al 2013, Girirajan et al 2013, Hardies et al 2013, Smigiel et al 2014, Casey et al 2015, Mitchell et al 2015, Rasmussen et al 2016, Kamath et al 2018, Kotalova et al 2018, Zhang et al 2021, Zhou et al 2021]. Individuals found to have this rare duplication were typically referred for testing because of intellectual disability and/or developmental delays, and occasionally because of multiple congenital anomalies. The 17q12 recurrent duplication likely also has reduced penetrance and variable expressivity since it is inherited in most instances from a parent with findings reported to be minimally abnormal or normal.
Table 2.
Frequency of Phenotypic Features in 86 Reported Individuals with 17q12 Recurrent Duplication
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| Phenotypic Feature | % of Persons with Feature |
|---|
| Intellectual disability | 71% |
| Speech delay | 65% |
| Gross motor delay | 49% |
| OFC <5th centile | 41% |
| Behavioral abnormalities | 62% |
| Seizures/epilepsy | 36% |
| Hypotonia | 73% |
| Other neurologic abnormalities | 85% |
| Height <5th centile | 22% |
| Ophthalmologic abnormalities | 28% |
| Weight <5th centile | 21% |
| Endocrine abnormalities | 26% |
| Weight >95th centile | 13% |
| Cardiac abnormalities | 14% |
| Renal abnormalities | 20% |
| Height >95th centile | 6% |
Developmental delay (DD) and intellectual disability (ID). Intellectual abilities range from normal to severe ID. The majority of affected individuals (71%) are reported to have delays or ID. However, the true incidence may be lower given variable expressivity and the ascertainment bias that is present due to the fact that most individuals who are found to have the 17q12 duplication are referred because of DD or ID. Speech delay is common (65%). Most affected individuals (49%-73%) have some degree of hypotonia and gross motor delay.
Behavioral and psychiatric conditions reported in a subset of affected individuals are autism spectrum disorder, schizophrenia, and behavioral abnormalities (including aggression, self-injurious behaviors, and compulsive disorders).
Seizures are reported in 36% of affected individuals.
Brain MRI occasionally reveals abnormalities including focal cortical dysplasia, agenesis of the corpus callosum, periventricular leukomalacia, and schizencephaly.
Microcephaly is reported in approximately 40% of individuals.
Eye and/or vision abnormalities including strabismus, astigmatism, amblyopia, cataract, coloboma, and microphthalmia occur in up to 28% of individuals.
Growth is variable. Both short (22%) and tall (6%) stature have been reported. Prenatal detection of short femur and humerus was reported in one fetus.
Endocrine abnormalities, reported in 26% of individuals, are variable and include diabetes insipidus, type 2 diabetes, growth hormone deficiency, hypoglycemia, hyponatremia and hyperkalemia, and pseudohypoaldosteronism.
Cardiac. The most common reported congenital heart defect is a small ventricular septal defect.
Renal abnormalities, present in approximately 20% of individuals, include horseshoe kidney, renal cysts, and hypoplastic kidneys.
Facial features. No specific dysmorphic features have been consistently observed. If present, dysmorphic features are nonspecific.
Other
Prevalence
In four studies of apparently unaffected controls, the 17q12 recurrent duplication was present in 1:2443 individuals [International Schizophrenia Consortium 2008, Itsara et al 2009, Shaikh et al 2009, Moreno-De-Luca et al 2010]. In a population study of 101,655 individuals from Iceland, the prevalence was 1:2,675 [Stefansson et al 2014].
In two different studies of individuals with intellectual disability, developmental delay or autism, the 17q12 recurrent duplication was reported in 5:2,034 (0.25%) individuals [Mitchell et al 2015] and 21:15,749 (0.13%) [Moreno-De-Luca et al 2010]; however, the frequency is much lower when accounting for all samples submitted in a clinical laboratory setting (19:22,231 [0.085%]) [Mitchell et al 2015].
In a cohort of individuals with schizophrenia, the 17q12 recurrent duplication was identified in 4:4,719 (0.08%) individuals [Szatkiewicz et al 2014].
