Clinical and Molecular Investigations Into Ciliopathies

Study Overview
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Brief Summary
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This study will evaluate patients ciliopathies. People with ciliopathies develop fibrocystic disease of the kidneys and liver, retinal degeneration, obesity, structural and functional defects of the central nervous system and the eyes, abnormal bone growth, abnormal sidedness of internal organs and polydactyly. The goal of the study is to better understand the medical complications of these disorders and identify characteristics that can help in the design of new treatments.

Detailed Description
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Human diseases caused by defects of the primary cilium (ciliopathies) are a group of distinct disorders with overlapping features. Clinical features of ciliopathies include fibrocystic disease of the kidneys and liver, retinal degeneration, obesity, structural and functional defects of the central nervous system and the eyes, abnormal bone growth, abnormal sidedness of internal organs and polydactyly. Human ciliopathies characterized by variable combinations of these features include autosomal recessive (ARPKD) and dominant (ADPKD) polycystic kidney diseases, nephronophthisis (NPHP), Joubert syndrome and related disorders (JSRD), Bardet-Biedl (BBS), Meckel-Gruber (MKS), Oral-Facial-Digital-type 1 (OFD1), and Alstrom syndromes (AS) and skeletal disorders such as Jeune syndrome (JS) and cleidocranial dysplasia. ARPKD, the most common pediatric ciliopathy, is characterized by cystic degeneration of the kidneys and congenital hepatic fibrosis of the liver. JSRD are a heterogenous group of syndromes characterized by a distinctive cerebellar and brainstem malformation (molar tooth sign), intellectual disability, abnormal eye movements, and abnormal respiratory pattern in infancy. Other common features seen in subsets of JSRD patients include, fibrocystic renal disease, congenital hepatic fibrosis, retinal degeneration, retinal colobomas, occipital encephalocele, and polydactyly. AS and BBS are ciliopathies characterized by obesity and retinal degeneration and hepatorenal disease in most cases. BBS patients also exhibit postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism and female genitourinary malformations. Additional features in AS include metabolic syndrome associated with insulin resistance and hyperlipidemia, cardiomyopathy and sensorineural deafness. OFD-I is characterized by polycystic kidney disease and oral, digital and brain anomalies including cerebellar hypoplasia with or without Dandy-Walker malformation. JS is a skeletal ciliopathy characterized by small thorax, short-limbed short stature, fibrocystic renal disease and retinal degeneration. The frequency and characteristics and natural history of specific organ/system disease in ciliopathies are either unknown or poorly defined, mostly because of the limited data available from retrospective reports of small numbers of patients.

Official Title
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Clinical and Molecular Investigations Into Ciliopathies

Conditions
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Ciliopathy

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Children and adults who carry a clinical diagnosis of a known ciliopathy such as ARPKD, CHF, JSRD, BBS, OFD1, AS and those patients who have typical features suggestive of a ciliopathy but not fulfilling the diagnostic criteria for any of the known disorders (unknown types of PKD and/or CHF, retinal degeneration, variants of molar tooth sign such as Dandy-Walker variants). This might rarely include adults who are unable to give informed consent. Among patients who have received a kidney or liver allograft, those with stable graft function and without severe transplantrelated complications are eligible for enrollment. EXCLUSION CRITERIA: Infants under 6 months of age Medically fragile patients who require frequent hospitalizations due to complications of end-stage renal disease (uncontrolled hypertension, severe electrolyte imbalances), hepatic disease (current variceal bleeding, overt encephalopathy, intractable recurrent cholangitis), severe cardiomyopathy as seen in some AS patients, or severe respiratory abnormalities as seen in some JSRD patients with severe brain stem involvement.

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ciliopathy<br>Children and adults who carry a clinical diagnosis of a known ciliopathy and those patients who have typical features suggestive of a cliopathy but not fulfilling the diagnostic criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ciliopathy | The general objective of this study is to assess the clinical characteristics of ciliopathies. | ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caroli's Syndrome, Congenital Hepatic Fibrosis, Ductal Plate Malformation, Polycystic Kidney, Autosomal Recessive Polycystic Kidney Disease, ARPKD, Kidney, Liver