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Clinical and Molecular Investigations Into Ciliopathies

6 Months
80 Years
Open (Enrolling)
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

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Trial Information

Clinical and Molecular Investigations Into Ciliopathies

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.

Inclusion Criteria


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

Type of Study:


Study Design:


Principal Investigator

Meral Gunay-Aygun, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Human Genome Research Institute (NHGRI)


United States: Federal Government

Study ID:




Start Date:

September 2003

Completion Date:

Related Keywords:

  • 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
  • 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
  • Kidney
  • Liver
  • Apraxias
  • Cysts
  • Liver Diseases
  • Fibrosis
  • Kidney Diseases
  • Polycystic Kidney Diseases
  • Oculocerebrorenal Syndrome
  • Orofaciodigital Syndromes
  • Polycystic Kidney, Autosomal Recessive
  • Caroli Disease
  • Liver Cirrhosis
  • Alstrom Syndrome
  • Cogan Syndrome
  • Coma
  • Optic Atrophies, Hereditary
  • Kidney Diseases, Cystic
  • Leber Congenital Amaurosis
  • Cerebellar Diseases
  • Eye Abnormalities
  • Bardet-Biedl Syndrome
  • Laurence-Moon Syndrome
  • Coloboma
  • Abnormalities, Multiple
  • Ataxia
  • Cholestasis



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