Management
To date, there are no cures for neurodevelopmental and skeletal ciliopathies, and treatment should be directed to alleviate the patients’ symptoms.
In JS, the following is recommended:
- Monitoring of respiratory problems in neonatal age (apnea/tachypnea), if severe hospitalization in intensive care units is required.
- Developmental surveillance with appropriate referral for rehabilitation and on-going support at and after school, especially for expressive speech difficulties.
- Management of seizures, if any.
- Surveillance by a development pediatrician or child psychiatrist for behavioral problems.
- Regular surveillance for extra-neurological involvement (retina, kidneys), at least once a year including nephrological, ophthalmological and hepatological assessment.
Renal and liver function and urinary concentration ability (measurement of urine osmolality) should be performed routinely after three years of age. Even in patients without abnormal laboratory findings, an abdominal ultrasound is indicated from two years of age, when renal or hepatic dysfunction typically starts to manifest. With regard to ophthalmic complications, external eye examinations should be routinely performed in children younger than three years of age, while screening for visual acuity and direct ophthalmoscope examination should be done at least once between three and five years of age. For a comprehensive and updated review on management of JS, please see the manuscript by Bachmann-Gagescu R et al. (2020) [JN1] listed in the Professionals – Publications section.
In JATD, the priority in management is to support respiratory function. In particular, patients with severe pulmonary insufficiency need chronic ventilator dependence, while milder cases may develop recurrent respiratory infections requiring appropriate antimicrobial therapy. Regardless of phenotype severity, patients should perform echocardiogram in order to rule out pulmonary hypertension. Several surgical procedures have recently been developed to correct thoracic abnormalities. Nevertheless, these procedures are considered controversial in the neonatal period, and risks and benefits must be carefully weighted in later ages. Because of the possible development of extra-skeletal abnormalities, children with JATD should be monitored through a multidisciplinary approach, including nephrological, ophthalmological and hepatological assessment, as for JS and other ciliopathies. For a review on JATD management, please see the manuscript by Poyner SE et al. (2013) listed in the Professionals – Publications section.
Genetic counseling
Mutations in CEP120 are inherited in an autosomal recessive manner. Affected individuals with an autosomal recessive ciliopathy related to the CEP120 gene have likely inherited the pathogenic variants from both unaffected parents. Thus, the recurrence risk for future pregnancies is 25%. Prenatal testing and preimplantation genetic diagnosis are feasible. No individual with homozygous CEP120 variants has been known to reproduce. The only recurrent variant (p.Ala199Pro) seems to consistently associate to a skeletal phenotype; besides this, genotype-phenotype correlates are scarce, and the phenotype is not predictable based on the type of mutation. There is usually a good degree of phenotypic consistency within ciliopathy families, albeit intra-familial variability cannot be excluded “a priori”, as this has been reported in some families carrying mutations in other ciliopathy genes.