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Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

ABSTRACT: Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by hypo-dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain malformation (molar tooth sign), and intellectual disability. We evaluated the neuropsychological profiles of 76 participants with JS in the context of molecular genetics and clinical covariates. Evaluations included neuropsychological testing, structured parental interviews, DNA sequencing, brain magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic examination, and assessment for renal and hepatic disease. On average, participants manifested Full Scale Intelligence Quotients (FSIQ) in the moderately to profoundly low range (M?=?64.3?±?15.3). Of the Wechsler index scores, verbal comprehension was least affected and processing speed was most affected. Receptive language was rated as better than expressive language on the Vineland Adaptive Behavior Scales-Second Edition. Those with abnormal EEG had a significantly lower FSIQ (n?=?15; M?=?50.7?±?12.9) compared to participants with normal EEG (n?=?39; M?=?64.7?±?16.3; p?=?.004). Participants taking psychiatric medications manifested a lower FSIQ (n?=?20; M?=?54.8?±?13.2) than those not taking them (n?=?42; M?=?65.0?±?17.2; p?=?.022). These correlations were also present in the TMEM67-related JS sub-cohort (n?=?14). Based on parental assessment, psychiatric and behavioral problems were significantly more common than in the general population for all measures (p?

SUBMITTER: Summers AC

PROVIDER: S-EPMC5682233 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

Summers Angela C AC Snow Joseph J Wiggs Edythe E Liu Alexander G AG Toro Camilo C Poretti Andrea A Zein Wadih M WM Brooks Brian P BP Parisi Melissa A MA Inati Sara S Doherty Dan D Vemulapalli Meghana M Mullikin Jim C JC Vilboux Thierry T Gahl William A WA Gunay-Aygun Meral M

American journal of medical genetics. Part A 20170512 7

Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by hypo-dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain malformation (molar tooth sign), and intellectual disability. We evaluated the neuropsychological profiles of 76 participants with JS in the context of molecular genetics and clinical covariates. Evaluations included neuropsychological testing, structured parental interviews, DNA sequencing, brain magnetic resonance imaging (MRI), electroencephal ...[more]

PMID: 28497568

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Project description:Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark is the molar tooth sign (MTS), a complex midbrain-hindbrain malformation visible on brain imaging, first recognized in JS. Estimates of the incidence of JSRD range between 1/80,000 and 1/100,000 live births, although these figures may represent an underestimate. The neurological features of JSRD include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation. These may be associated with multiorgan involvement, mainly retinal dystrophy, nephronophthisis, hepatic fibrosis and polydactyly, with both inter- and intra-familial variability. JSRD are classified in six phenotypic subgroups: Pure JS; JS with ocular defect; JS with renal defect; JS with oculorenal defects; JS with hepatic defect; JS with orofaciodigital defects. With the exception of rare X-linked recessive cases, JSRD follow autosomal recessive inheritance and are genetically heterogeneous. Ten causative genes have been identified to date, all encoding for proteins of the primary cilium or the centrosome, making JSRD part of an expanding group of diseases called "ciliopathies". Mutational analysis of causative genes is available in few laboratories worldwide on a diagnostic or research basis. Differential diagnosis must consider in particular the other ciliopathies (such as nephronophthisis and Senior-Loken syndrome), distinct cerebellar and brainstem congenital defects and disorders with cerebro-oculo-renal manifestations. Recurrence risk is 25% in most families, although X-linked inheritance should also be considered. The identification of the molecular defect in couples at risk allows early prenatal genetic testing, whereas fetal brain neuroimaging may remain uninformative until the end of the second trimester of pregnancy. Detection of the MTS should be followed by a diagnostic protocol to assess multiorgan involvement. Optimal management requires a multidisciplinary approach, with particular attention to respiratory and feeding problems in neonates and infants. Cognitive and behavioral assessments are also recommended to provide young patients with adequate neuropsychological support and rehabilitation. After the first months of life, global prognosis varies considerably among JSRD subgroups, depending on the extent and severity of organ involvement.

Dataset Information

Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

Publications

Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.

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