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  • ciliopathies refers to a group of conditions characterised by impaired cilia function
  • normal ciliary beat frequency is 1000-1500 beats per minute.
  • the frequency is slower in the peripheral airways (eg, bronchioles) compared to the larger airways (eg, trachea).
  • the ciliary motility is maintained in the same plane along the length of airways and results in mucociliary transport rates up to 20-30 mm/min.
  • normal individuals produce 500ml sputum per day which is swallowed.

immotile cilia syndrome

  • primary ciliary dyskinesia (PCD)
  • a group of genetic disorders with extensive genetic heterogeneity (although most appear to be autosomal recessive, X-linked inheritance patterns have also been described) characterized by abnormal ciliary motion and impaired mucociliary clearance
  • 2 main genes implicated are DNAI1 and DNAH5, which encode for components of the outer dynein arm complex, although 11 genes with disease-causing mutations have been identified.
  • prevalence of PCD in USA is approximately 1:16,000 live births
  • this leads to recurrent or persistent respiratory infections, sinusitis, rhinitis, otitis media, pneumonia and male infertility.
    • NB. Young's syndrome also causes chronic sinopulmonary infections and male infertility but apparently cilia on histology are normal
  • some may have impaired leukocyte function
  • evidence of female infertility is inconclusive.
  • some may develop hydrocephalus or chronic headaches - explained by the fact that ependymal cells are ciliated
  • in 50% of the patients, ICS is associated with situs inversus and such patients are classified as having Kartagener's syndrome:
    • autosomal recessive genetic condition with triad of situs inversus (ie. dextrocardia), chronic sinusitis, and bronchiectasis
    • symptoms result from defective cilia motility
  • until now physiotherapy and antibiotics were the only treatment but there is hope that gene therapy may be useful:

Bardet-Biedl syndrome (BBS)

  • prevalence of 1 in 140,000 to 1 in 160,000 in USA but more common in the Bedouin population of Kuwait, affecting about 1 in 13,500 newborns, and on the island of Newfoundland (off the east coast of Canada), where it affects an estimated 1 in 17,000 newborns.
  • result from mutations in at least 14 different genes (often called BBS genes) which effect cilia function.
  • it is typically autosomal recessive
  • clinical features may include:
    • rod–cone dystrophy with night blindness and progressive blindness in childhood
    • childhood truncal obesity which progresses into adulthood and risks diabetes mellitus, etc.
    • polydactyly, intellectual disability or learning problems, and abnormalities of the genitalia
    • hypogonadism and male infertility
    • impaired speech, delayed development of motor skills such as standing and walking, behavioral problems such as emotional immaturity and inappropriate outbursts, and clumsiness or poor coordination
    • distinctive facial features, dental abnormalities, unusually short or fused fingers and/or toes, and a partial or complete loss of the sense of smell (anosmia) have also been reported in some people
    • can affect the heart, liver, and digestive system1)
    • see also wikipedia

cystic kidney diseases

  • most cystic kidney diseases are caused by genetic mutations resulting in cilia dysfunction
  • polycystin-1 and -2, encoded by PKD1 and PKD2, where mutations lead to autosomal-dominant polycystic kidney disease (ADPKD) which may also cause polycystic liver disease
  • fibrocystin/polyductin, encoded by PKHD1, where mutations lead to autosomal-recessive polycystic kidney disease (ARPKD)
  • uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies2):
    • medullary cystic kidney disease type 2 (MCKD2)
    • familial juvenile hyperuricemic nephropathy
    • glomerulocystic kidney disease
  • nephronophthisis (NPHP)
    • an autosomal recessive genetically heterogenic disorder with identified mutations in a number of genes that encode proteins involved in the function of primary cilia, basal bodies, and centrosomes
    • usually progress to ESRF by young adulthood accounting for 2.5-15% of juvenile renal dialysis patients
    • 3 variants with different age of onset of ESRF
    • may have abnormalities in extrarenal organs including hepatic fibrosis and retinal defects are often present and are usually also associated with a specific gene defect

Meckel-Gruber syndrome

  • a rare, lethal, ciliopathic, autosomal recessive genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations, polydactyly, hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.3)

Joubert syndrome

  • a rare genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination
  • the most common features include ataxia (lack of muscle control), hyperpnea (abnormal breathing patterns), sleep apnea, abnormal eye and tongue movements, and hypotonia

Alstrom syndrome

  • It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries.
ciliopathies.txt · Last modified: 2014/04/07 04:25 by

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