Clinical and Molecular Investigations Into Ciliopathies
Condition: Ciliopathy
MeSH terms: Ciliopathies
Study type: Observational

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.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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).
      
Keywords: Caroli's Syndrome; Congenital Hepatic Fibrosis; Ductal Plate Malformation; Polycystic Kidney; Autosomal Recessive Polycystic Kidney Disease; ARPKD; Kidney; Liver