Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome

Tan, Tiong Yang; Aftimos, Salim; Worgan, Lisa; Susman, Rachel; Wilson, Meredith; Ghedia, Sondhya; Kirk, Edwin P.; Love, Donald R.; Ronan, Anne; Darmanian, Artur; Slavotinek, Anne; Hogue, Jacob S.; Moeschler, John B.; Ozmore, Jillian R; Widmer, Richard P; Savarirayan, Ravi; Peters, Gregory B.

doi:10.1136/jmg.2008.065391

Cited by 64 publications

(78 citation statements)

References 13 publications

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“…These features have also been reported previously in addition to communicating hydrocephalus, periventricular white matter changes, 13,22,29 and partial pituitary stalk interruption syndrome. 19 Case 35 presented with a Chiari type 1 malformation, which has also been described by Terrone et al, 23 co existing with a mild anomaly of the medulla oblongata.…”

Section: Growth Parameterssupporting

confidence: 85%

“…This is similar to numbers in the medical literature (18-29%). 13,18,22 Postnatal growth retardation is present in 35%, which is also similar to the other larger cohorts of patients (18-36%). 13,22 Short stature, if present, was proportionate.…”

Section: Growth Parameterssupporting

confidence: 84%

“…13,18,22 Postnatal growth retardation is present in 35%, which is also similar to the other larger cohorts of patients (18-36%). 13,22 Short stature, if present, was proportionate. In the current cohort, case 17 with a 17q21.31 deletion and case 42 with a KANSL1 variant had (partial) growth hormone deficiency, which has been reported previously.…”

Section: Growth Parameterssupporting

confidence: 84%

“…13,18,20,22,30 In our cohort, we observed behavioural problems in 57% of cases. These problems included autism/autistic traits, ADHD/attention deficit/ hyperactivity, shyness, anxiety/phobias, impulsive and stereotypic behaviour, psychosis, and depression.…”

Section: Neuropsychological Disorderssupporting

confidence: 49%

“…A search of the medical literature identified 23 articles describing the clinical features of 81 patients with KdVS. [1][2][3][4][5]13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

Section: Methodsmentioning

confidence: 99%

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The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

et al. 2015

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The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

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Section: Growth Parameterssupporting

confidence: 85%

Section: Growth Parameterssupporting

confidence: 84%

Section: Growth Parameterssupporting

confidence: 84%

Section: Neuropsychological Disorderssupporting

confidence: 49%

Section: Methodsmentioning

confidence: 99%

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The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

et al. 2015

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De novo triplication of the MAPT gene from the recurrent 17q21.31 microdeletion region in a patient with moderate intellectual disability and various minor anomalies

Gregor

Krumbiegel

Kraus

et al. 2012

American J of Med Genetics Pt A

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We report on a 16-year-old male patient with moderate intellectual disability, behavioral problems, and further anomalies such as facial dysmorphism, heart defect, and urogenital anomalies. By molecular karyotyping we identified the first de novo copy number gain to four copies on chromosome 17q21.31 including the MAPT gene but not the entire recurrent microdeletion/microduplication region. Recurrent microdeletions of this region including the MAPT and the CHRH1 genes have been shown to be a relatively frequent cause of intellectual disability, while only a few reciprocal duplications in patients with variable cognitive disorders have been published so far. A common inversion polymorphism in this region has been linked to a distinct H2 haplotype and seems to be associated with an increased risk for microdeletions and -duplications. Our patient and his father were both heterozygous for the H1/H2 haplotype, whereas the mother was homozygous for the H2 haplotype. In our patient the dosage gain apparently occurred on the paternal H1 allele and did not involve the H2 allele as in the previously published cases. This patient further delineates the genotypic and phenotypic variability associated with copy number variants from the 17q21.31 microdeletion region.

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Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome

Egger

Wingbermühle

Verhoeven

et al. 2012

American J of Med Genetics Pt A

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The 17q21.31 microdeletion syndrome with its characteristic features including developmental delay, moderate intellectual disability, facial dysmorphisms, and anomalies of the brain and multiple organ systems was recently described. As to its behavioral profile, scarce data from clinical observations have suggested a remarkably amiable, friendly disposition, to some extent comparable to that observed in Angelman and Williams syndromes. The present study focuses on the various aspects of neurocognitive functioning, particularly social cognition, in patients with 17q21.31 microdeletion syndrome. Neuropsychological assessment was performed in three out of the four known Dutch patients with a genetically proven 17q21.31 microdeletion syndrome. Apart from developmental age, cognition and social-emotional functioning was extensively assessed. In addition, data of three intellectually disabled physically healthy reference subjects, recruited from a small outpatient sample, were included. The general cognitive profile of all subjects was in accordance with their lowered intellectual capacities, albeit that in patients with the 17q21.31 microdeletion, a relatively strong memory for social-contextual information was found. Basic emotion perception was intact, but patients with the 17q21.31 microdeletion syndrome showed less social fear and more approaching behavior. Interestingly, alexithymic traits, that is marked difficulties in the recognition and expression of emotions, were more prevalent in reference subjects. Despite the methodological limitations characteristic for research in people with intellectual disabilities, with a neuropsychological assessment strategy, in three patients with 17q21.31 microdeletion syndrome, preliminary evidence for hypersocial behavior with a high level of frustration tolerance was found that may be implicated in its behavioral phenotype.

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Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome

Abstract: These data have significant implications for the clinical diagnosis and management of other individuals with 17q21.31 deletions.

Cited by 64 publications

References 13 publications

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

De novo triplication of the MAPT gene from the recurrent 17q21.31 microdeletion region in a patient with moderate intellectual disability and various minor anomalies

Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome

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