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Clinical and Molecular Investigations Into Ciliopathies

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ) Identifier:
First received: September 10, 2003
Last updated: November 11, 2014
Last verified: January 2014

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....

Autosomal Recessive Polycystic Kidney Disease
Congenital Hepatic Fibrosis
Caroli's Disease
Polycystic Kidney Disease
Joubert Syndrome
Cerebro-Oculo-Renal Syndromes
COACH Syndrome
Senior-Loken Syndrome
Dekaban-Arima Syndrome
Cogan Oculomotor Apraxia
Bardet-Biedl Syndrome
Alstrom Syndrome
Oral-Facial-Digital Syndrome

Study Type: Observational
Official Title: Clinical and Molecular Investigations Into Ciliopathies

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 500
Study Start Date: September 2003
Detailed Description:

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.

In this protocol, we will evaluate up to 500 children and adults with various ciliopathies with special emphasis on delineating the characteristics of individual organ system involvement including kidney, liver, eye, central nervous system and bone disease and metabolic derangements associated with obesity/insulin resistance/metabolic syndrome. We will perform mutation analysis of the related ciliopathy genes as needed. Routine outpatient evaluations will last 4-5 days and follow up visits will occur approximately every 1-2 years. This protocol will provide longitudinal information regarding progression of individual organ system disease in a large cohort of ciliopathy patients, and will elucidate genotype-phenotype correlations. The protocol will also allow the investigators to acquire sufficient expertise in relatively common ciliopathies such as ARPKD, JSRD and AS to design therapeutic interventions for specific organ diseases in the future.


Ages Eligible for Study:   6 Months to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

This protocol will enroll children and adults who carry a clinical diagnosis of ARPKD, CHF, JSRD, BBS, OFD or AS and who has either PKD/NP spectrum of changes in the kidneys or CHF/Caroli s syndrome of the liver. 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 transplant-related complications are eligible for enrollment. Patients and their parents/legal guardians must be willing to come to the NIH Clinical Center for admission annually.


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) or hepatic disease (current variceal bleeding, overt encephalopathy, intractable recurrent cholangitis).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00068224

Contact: Meral Gunay-Aygun, M.D. (443) 286-1703

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Principal Investigator: Meral Gunay-Aygun, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ) Identifier: NCT00068224     History of Changes
Other Study ID Numbers: 030264, 03-HG-0264
Study First Received: September 10, 2003
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Caroli's Syndrome
Congenital Hepatic Fibrosis
Ductal Plate Malformation
Polycystic Kidney
Polycystic Liver
Molar Tooth Sign
Dandy-Walker Malformation
Situs Inversus
Cerebellar Vermis Hypoplasia
Autosomal Recessive Polycystic Kidney Disease

Additional relevant MeSH terms:
Alstrom Syndrome
Bardet-Biedl Syndrome
Caroli Disease
Cerebellar Diseases
Cogan Syndrome
Genetic Diseases, Inborn
Kidney Diseases
Kidney Diseases, Cystic
Laurence-Moon Syndrome
Leber Congenital Amaurosis
Liver Cirrhosis
Multicystic Dysplastic Kidney
Oculocerebrorenal Syndrome
Optic Atrophies, Hereditary
Orofaciodigital Syndromes
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Recessive
Abnormalities, Multiple
Amino Acid Transport Disorders, Inborn
Bile Duct Diseases
Biliary Tract Diseases
Bone Diseases
Bone Diseases, Developmental
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn processed this record on November 24, 2014