OMIM ID:
Joubert Syndrome and Related Disorders
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ocular findings like systemic features are highly variable both within and between families. Vision can be normal but in other patients it is severely reduced to the range of 20/200. The pupils may respond sluggishly or even paradoxically to light. ERG recordings have been reported to be normal in some patients, but absent or reduced in others. The fundus appearance is often normal but in other individuals the pigmentation is mottled, the retinal arterioles are attenuated, and the macula has a cellophane maculopathy. Drusen and colobomas are sometimes seen in the optic nerve while occasional patients have typical chorioretinal colobomas. The eyebrows are often highly arched.
The oculomotor system is frequently involved. Apraxia to some degree is common with most patients having difficulty with smooth pursuit and saccadic movements. Compensatory head thrusting is often observed. A pendular nystagmus may be present while esophoria or esotropia is present in many patients.
Systemic Features
There is a great deal of clinical heterogeneity in this group of ciliary dyskinesias. Developmental delays, cognitive impairment, truncal ataxia, breathing irregularities, and behavioral disorders are among the more common features. Hyperactivity and aggressiveness combined with dependency require constant vigilance and care. Postaxial polydactyly is a feature of some cases. Hypotonia is evident at birth. Liver failure and renal disease develop in many individuals. Neuroimaging of the midbrain-hindbrain area reveals agenesis or some degree of dysgenesis of the vermis with the ‘molar tooth sign’ in the isthmus region considered to be a diagnostic sign. The fourth ventricle is usually enlarged while the cerebellar hemispheres may be hypoplastic.
The facies features are said to be distinctive in older individuals. The face appears long with frontal prominence due to bitemporal narrowing, the nasal bridge and tip are prominent, the jaw is prominent, the lower lip protrudes, and the corners of the mouth are turned down.
Genetics
Inheritance
This is a clinically and genetically heterogeneous group of disorders with many overlapping features. Most disorders in this disease category, known as JSRD, are inherited in an autosomal recessive pattern. Mutations in at least 34 genes have been identified. One, OFD1 (300804), is located on the X chromosome (Xp22.2).
There are significant clinical similarities to Meckel syndrome (249000) and Smith-Lemli-Opitz syndrome (270400).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.