17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome

Bernardo, Pia; Madia, Francesca; Santulli, Lia; Gaudio, Luigi Del; Caccavale, Ciro; Zara, Federico; Traverso, Monica; Cirillo, Mario; Striano, Salvatore; Coppola, Antonietta

doi:10.1016/j.braindev.2016.02.002

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…Most cases of KdVS are diagnosed in infancy when a comparative genomic hybridization (CGH) microarray is ordered by a pediatrician or clinical geneticist due to dysmorphic features, hypotonia, developmental delay, and multisystem abnormalities. However, the nonneurologic abnormalities may be subtle in some cases and a microarray not considered prior to seizure onset . Testing may be considered in cases of Panayiotopoulos syndrome or CECTS, if the patient has developmental delay, dysmorphic features, or suggestive MRI findings.…”

Section: Discussionmentioning

confidence: 99%

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The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

et al. 2017

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The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence.

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Section: Discussionmentioning

confidence: 99%

“…However, the nonneurologic abnormalities may be subtle in some cases and a microarray not considered prior to seizure onset. 25 Testing may be considered in cases of Panayiotopoulos syndrome or CECTS, if the patient has developmental delay, dysmorphic features, or suggestive MRI findings.…”

Section: Discussionmentioning

confidence: 99%

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

et al. 2017

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“…Cleft palate and hearing loss (conductive or sensorineural) may also occur, but are less common [6,7]. Communication deficits have also been observed as part of the complex profile seen in KdVS [6,8,9]. Based on a limited number of case reports, expressive communication is suggested to be severely impaired in the preschool years, characterised by a striking late onset of first words (as late as 3 years of age) and a need for therapy in both verbal and nonverbal domains (e.g., sign language, aided communication, such as computer touch screens) [5,6,8,10].…”

Section: Introductionmentioning

confidence: 99%

Early speech development in Koolen de Vries syndrome limited by oral praxis and hypotonia

et al. 2017

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Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its specific symptomatology has not been examined, limiting prognostic counselling and application of targeted therapies. Here we examine the communication phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1 variants, 25 with 17q21.31 microdeletion), aged 1.0-27.0 years were assessed for oral-motor, speech, language, literacy, and social functioning. Early history included hypotonia and feeding difficulties. Speech and language development was delayed and atypical from onset of first words (2; 5-3; 5 years of age on average). Speech was characterised by apraxia (100%) and dysarthria (93%), with stuttering in some (17%). Speech therapy and multi-modal communication (e.g., sign-language) was critical in preschool. Receptive and expressive language abilities were typically commensurate (79%), both being severely affected relative to peers. Children were sociable with a desire to communicate, although some (36%) had pragmatic impairments in domains, where higher-level language was required. A common phenotype was identified, including an overriding 'double hit' of oral hypotonia and apraxia in infancy and preschool, associated with severely delayed speech development. Remarkably however, speech prognosis was positive; apraxia resolved, and although dysarthria persisted, children were intelligible by mid-to-late childhood. In contrast, language and literacy deficits persisted, and pragmatic deficits were apparent. Children with KdVS require early, intensive, speech motor and language therapy, with targeted literacy and social language interventions as developmentally appropriate. Greater understanding of the linguistic phenotype may help unravel the relevance of KANSL1 to child speech and language development.

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“…According to the authors, peculiar genes within the 17q21.31 microdeletion conferring some seizure susceptibility and the haploinsufficiency of the CRH1 gene may predispose to having seizures, especially infantile spasms [Wray, 2013;Bernardo et al, 2016]. Furthermore, CRHR1 signaling is involved in memory and learning, and a dosage deficit of this gene may contribute to the presence of global developmental delay [Sharkey et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other phenotypic features were observed including scoliosis/ kyphosis in 36% of the patients with this microdeletion, cryptorchidism (78%), kidney and urological anomalies (32%), as well as epilepsy described in more than 55% of the individuals [Bernardo et al, 2016]. The prevalence of KDVS varies from 1 in 13,000 and 1 in 20,000, identified as a de novo event [Egger et al, 2013].…”

Section: Novel Insightsmentioning

confidence: 99%

Molecular Characterization of Koolen De Vries Syndrome in Two Girls with Idiopathic Intellectual Disability from Central Brazil

Nascimento¹,

Pinto²,

Melo³

et al. 2017

Mol Syndromol

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Koolen de Vries syndrome (KDVS; MIM 610443) is a genomic disorder caused by a recurrent microdeletion derived from nonallelic homologous recombination mediated by flanking segmental duplications. Clinical manifestations of this syndrome are characterized by intellectual disability, hypotonia, a friendly behavior, distinctive facial features, and epilepsy. Herein, we report a case of 2 girls who revealed global developmental delay, mild facial dysmorphisms, friendly behavior, and epileptic seizure with a de novo 17q21.31 microdeletion detected by chromosomal microarray analysis (CMA). Conventional cytogenetics analysis by GTG-banding showed a female karyotype 46,XX for both girls. CMA revealed a microdeletion spanning approximately 500 kb in 17q21.31 in both girls, encompassing the following genes: CRHR1, MGC57346, CRHR1-IT1, MAPT-AS1, SPPL2C, MAPT, MAPT-IT1, STH, and KANSL1. Haploinsufficiency of one or more of these genes within the deleted region is the most probable cause of the probands' phenotype and is responsible for the phenotype seen in KDVS. CMA is a powerful diagnostic tool and an effective method to identify the de novo 17q21.31 microdeletion associated with KDVS in our probands.

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17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome

Cited by 8 publications

References 12 publications

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

Early speech development in Koolen de Vries syndrome limited by oral praxis and hypotonia

Molecular Characterization of Koolen De Vries Syndrome in Two Girls with Idiopathic Intellectual Disability from Central Brazil

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