Clinical and Molecular Investigations Into Ciliopathies - Full Text View

Purpose

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....

Condition
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 Nephronophthisis 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:

Genetics Home Reference related topics: Alström syndrome Bardet-Biedl syndrome branchio-oculo-facial syndrome Charcot-Marie-Tooth disease coloboma congenital hepatic fibrosis cranioectodermal dysplasia Crouzon syndrome Dandy-Walker syndrome hereditary neuropathy with liability to pressure palsies Joubert syndrome Leber congenital amaurosis Lenz microphthalmia syndrome Lowe syndrome lysinuric protein intolerance Miller syndrome nephronophthisis North American Indian childhood cirrhosis oculofaciocardiodental syndrome oral-facial-digital syndrome polycystic kidney disease retinitis pigmentosa Senior-Løken syndrome succinic semialdehyde dehydrogenase deficiency tetrasomy 18p

MedlinePlus related topics: Coma

Genetic and Rare Diseases Information Center resources: Alström Syndrome Apraxia Autosomal Recessive Polycystic Kidney Disease Bardet-Biedl Syndrome Bardet-Biedl Syndrome 12 Bile Duct Cysts COACH Syndrome Caroli Disease Charcot-Marie-Tooth Disease Cogan's Syndrome Cone-rod Dystrophy Cone-rod Dystrophy 2 Congenital Hepatic Fibrosis Hereditary Neuropathy With Liability to Pressure Palsy Heterotaxy Joubert Syndrome Joubert Syndrome With Oculorenal Anomalies Leber Congenital Amaurosis Lowe Oculocerebrorenal Syndrome Medullary Cystic Kidney Disease Miller Syndrome Orofaciodigital Syndromes Pigmentary Retinopathy Retinitis Pigmentosa Roussy Levy Syndrome Senior Loken Syndrome Situs Inversus X-linked Visceral Heterotaxy 1

U.S. FDA Resources

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.

Eligibility


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

Criteria

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.

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 ClinicalTrials.gov identifier: NCT00068224

Contacts


Contact: Meral Gunay-Aygun, M.D.	(443) 286-1703	mg466r@nih.gov

Locations


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 prpl@mail.cc.nih.gov

Sponsors and Collaborators

National Human Genome Research Institute (NHGRI)

Investigators


Principal Investigator:	Meral Gunay-Aygun, M.D.	National Human Genome Research Institute (NHGRI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman M, Graf J, Bryant JC, Kleta R, Garcia A, Edwards H, Piwnica-Worms K, Adams D, Bernardini I, Fischer RE, Krasnewich D, Oden N, Ling A, Quezado Z, Zak C, Daryanani KT, Turkbey B, Choyke P, Guay-Woodford LM, Gahl WA. Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol. 2010 Jun;5(6):972-84. doi: 10.2215/CJN.07141009. Epub 2010 Apr 22.

Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):296-306. doi: 10.1002/ajmg.c.30225. Review.

Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gerstein M, Piwnica-Worms K, Choyke P, Daryanani KT, Turkbey B, Fischer R, Bernardini I, Sincan M, Zhao X, Sandler NG, Roque A, Douek DC, Graf J, Huizing M, Bryant JC, Mohan P, Gahl WA, Heller T. Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology. 2013 Jan;144(1):112-121.e2. doi: 10.1053/j.gastro.2012.09.056. Epub 2012 Oct 3.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Brien K, Font-Montgomery E, Lukose L, Bryant J, Piwnica-Worms K, Edwards H, Riney L, Garcia A, Daryanani K, Choyke P, Mohan P, Heller T, Gahl WA, Gunay-Aygun M. Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):83-9. doi: 10.1097/MPG.0b013e318228330c.

Gunay-Aygun M, Parisi MA, Doherty D, Tuchman M, Tsilou E, Kleiner DE, Huizing M, Turkbey B, Choyke P, Guay-Woodford L, Heller T, Szymanska K, Johnson CA, Glass I, Gahl WA. MKS3-related ciliopathy with features of autosomal recessive polycystic kidney disease, nephronophthisis, and Joubert Syndrome. J Pediatr. 2009 Sep;155(3):386-92.e1. doi: 10.1016/j.jpeds.2009.03.045. Epub 2009 Jun 21.


Responsible Party:	National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier:	NCT00068224 History of Changes
Other Study ID Numbers:	030264, 03-HG-0264
Study First Received:	September 10, 2003
Last Updated:	January 6, 2015
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 Ciliopathy Polycystic Kidney Polycystic Liver Nephronophthisis Molar Tooth Sign Dandy-Walker Malformation	Retinopathy Situs Inversus Heterotaxia Cerebellar Vermis Hypoplasia Autosomal Recessive Polycystic Kidney Disease ARPKD Kidney Liver

Additional relevant MeSH terms:


Alstrom Syndrome Bardet-Biedl Syndrome Cogan Syndrome Laurence-Moon Syndrome Oculocerebrorenal Syndrome Orofaciodigital Syndromes Syndrome Central Nervous System Diseases Digestive System Abnormalities Digestive System Diseases Heredodegenerative Disorders, Nervous System Nervous System Diseases Nervous System Malformations Peripheral Nervous System Diseases Vasculitis	Caroli Disease Cerebellar Diseases Coloboma Coma Fibrosis Genetic Diseases, Inborn Kidney Diseases Kidney Diseases, Cystic Leber Congenital Amaurosis Liver Cirrhosis Multicystic Dysplastic Kidney Optic Atrophies, Hereditary Polycystic Kidney Diseases Polycystic Kidney, Autosomal Recessive Abnormalities, Multiple

ClinicalTrials.gov processed this record on February 26, 2015