Clinical and Molecular Investigations Into Ciliopathies - Full Text View

Study Description

Brief Summary:

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 or disease
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

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.

Study Design


Study Type :	Observational
Actual Enrollment :	326 participants
Official Title:	Clinical and Molecular Investigations Into Ciliopathies
Study Start Date :	September 8, 2003

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Bardet-Biedl syndrome Dandy-Walker malformation Senior-Løken syndrome Congenital hepatic fibrosis Cranioectodermal dysplasia Oral-facial-digital syndrome Polycystic kidney disease

Genetic and Rare Diseases Information Center resources: Bardet-Biedl Syndrome Bardet-Biedl Syndrome 1 Bardet-Biedl Syndrome 10 Bardet-Biedl Syndrome 11 Bardet-Biedl Syndrome 12 Bardet-Biedl Syndrome 2 Laurence-Moon Syndrome Apraxia AlstrÃ¶m Syndrome Cogan's Syndrome Autosomal Recessive Polycystic Kidney Disease Lowe Oculocerebrorenal Syndrome Heterotaxy Congenital Hepatic Fibrosis Orofaciodigital Syndromes Nephronophthisis Joubert Syndrome Caroli Disease Joubert Syndrome With Oculorenal Anomalies Situs Inversus Senior Loken Syndrome COACH Syndrome Miller Syndrome Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsy Roussy Levy Syndrome Cone-rod Dystrophy Cone-rod Dystrophy 2 Retinitis Pigmentosa Bile Duct Cysts

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	6 Months to 80 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00068224

Locations


United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

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.

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

Boerwinkle C, Marshall JD, Bryant J, Gahl WA, Olivier KN, Gunay-Aygun M. Respiratory manifestations in 38 patients with Alström syndrome. Pediatr Pulmonol. 2017 Apr;52(4):487-493. doi: 10.1002/ppul.23607. Epub 2016 Dec 28.

Vilboux T, Malicdan MC, Chang YM, Guo J, Zerfas PM, Stephen J, Cullinane AR, Bryant J, Fischer R, Brooks BP, Zein WM, Wiggs EA, Zalewski CK, Poretti A, Bryan MM, Vemulapalli M, Mullikin JC, Kirby M, Anderson SM; NISC Comparative Sequencing Program, Huizing M, Toro C, Gahl WA, Gunay-Aygun M. Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects. J Med Genet. 2016 May;53(5):318-29. doi: 10.1136/jmedgenet-2015-103416. Epub 2016 Jan 13.

Malicdan MC, Vilboux T, Stephen J, Maglic D, Mian L, Konzman D, Guo J, Yildirimli D, Bryant J, Fischer R, Zein WM, Snow J, Vemulapalli M, Mullikin JC, Toro C, Solomon BD, Niederhuber JE; NISC Comparative Sequencing Program, Gahl WA, Gunay-Aygun M. Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a hybrid ciliopathy with overlapping features of Jeune and Joubert syndromes. J Med Genet. 2015 Dec;52(12):830-9. doi: 10.1136/jmedgenet-2015-103316. Epub 2015 Sep 18.

Banks N, Bryant J, Fischer R, Huizing M, Gahl WA, Gunay-Aygun M. Pregnancy in autosomal recessive polycystic kidney disease. Arch Gynecol Obstet. 2015 Mar;291(3):705-8. doi: 10.1007/s00404-014-3445-8. Epub 2014 Sep 12.

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 Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier:	NCT00068224 History of Changes
Other Study ID Numbers:	030264 03-HG-0264
First Posted:	September 10, 2003 Key Record Dates
Last Update Posted:	March 29, 2018
Last Verified:	November 13, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):


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:


Syndrome Fibrosis Kidney Diseases Polycystic Kidney Diseases Apraxias Bardet-Biedl Syndrome Laurence-Moon Syndrome Alstrom Syndrome Cogan Syndrome Polycystic Kidney, Autosomal Recessive Liver Cirrhosis Genetic Diseases, Inborn Ciliopathies Orofaciodigital Syndromes Coma	Oculocerebrorenal Syndrome Caroli Disease Disease Pathologic Processes Urologic Diseases Kidney Diseases, Cystic Abnormalities, Multiple Congenital Abnormalities Psychomotor Disorders Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms Hypothalamic Diseases Brain Diseases