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:
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)
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.