Joubert syndrome with oculorenal anomalies

Other Names: Arima syndrome; Cerebro-oculo-hepato-renal syndrome; Dekaban Arima syndrome; Chorioretinal coloboma with cerebellar vermis aplasia; Joubert syndrome 5; Joubert syndrome with bilateral chorioretinal coloboma; Cerebello-oculo-renal syndrome; CORS; Dekaban-Arima syndrome; Joubert syndrome with oculorenal defect; Joubert syndrome with Senior-Loken syndrome; JS type B; JS-OR; Cerebellooculorenal syndrome

A rare subtype of Joubert syndrome (JS) and related disorders (JSRD) characterized by the neurological features of JS associated with both renal and ocular disease.

Epidemiology

Prevalence is unknown.

Cause

About 50% of patients carry mutations in the CEP290 gene (12q21.33).

Inheritance

Autosomal recessive inheritance, a 25% chance

It is transmitted in an autosomal recessive manner.

Signs and symptoms

Patients present retinal involvement (manifesting with either Leber congenital amaurosis (LCA, ), or progressive retinal dystrophy) and nephronophthisis (NPH, usually juvenile). Retinal involvement is present at birth (LCA) or may manifest later in life. Juvenile NPH usually becomes clinically symptomatic towards the late first decade or the early second decade of life. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Apnea
• Ataxia
• Cerebellar vermis hypoplasia
• Global developmental delay
• Intellectual disability(Mental deficiency)
• Molar tooth sign on MRI
• Muscular hypotonia(Low or weak muscle tone)
• Nephropathy
• Retinal dystrophy(Breakdown of light-sensitive cells in back of eye)
• Tachypnea(Increased respiratory rate or depth of breathing)

30%-79% of people have these symptoms

• Autistic behavior
• Biparietal narrowing
• Blindness
• Chorioretinal coloboma(Birth defect that causes a hole in the innermost layer at the back of the eye)
• Iris [[coloboma](Cat eye)
• Long face(Elongation of face)
• Low-set, posteriorly rotated ears
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Ptosis(Drooping upper eyelid)

5%-29% of people have these symptoms

• Abnormality of cardiovascular system morphology
• Abnormality of neuronal migration
• Abnormality of the hypothalamus-pituitary axis
• Aganglionic megacolon(Enlarged colon lacking nerve cells)
• Anteverted nares(Nasal tip, upturned)
• Aplasia/Hypoplasia of the corpus callosum
• Encephalocele
• Foot polydactyly(Duplication of bones of the toes)
• Hand polydactyly(Extra finger)
• Highly arched eyebrow(Arched eyebrows)
• Hydrocephalus(Too much cerebrospinal fluid in the brain)
• Prominent nasal bridge(Elevated nasal bridge)
• Renal insufficiency(Renal failure)
• Scoliosis
• Seizure
• Strabismus(Cross-eyed)

Diagnosis

The disorder is characterized by absence or underdevelopment of the cerebellar vermis and a malformed brain stem (molar tooth sign), both of which can be visualized on a transverse view of head MRI scan. Together with this sign, the diagnosis is based on the physical symptoms and genetic testing for mutations. If the gene mutations have been identified in a family member, prenatal or carrier diagnosis can be pursued.

Treatment

Treatment for Joubert syndrome is symptomatic and supportive. Infants with abnormal breathing patterns should be monitored. The syndrome is associated with progressive worsening for kidneys, the liver and the eyes and thus requires regular monitoring. Delays in gross motor skills, fine motor skills and speech development are seen in almost all individuals with Joubert syndrome. Delays can be due to low muscle tone as well as impaired motor coordination. Some children have also been noted to have visual impairment due to abnormal eye movements. Developmental delays are usually treated with physical therapy, occupational therapy, and speech therapy interventions. Most children diagnosed with Joubert syndrome are able to achieve standard milestones, although often at a much later age.

NIH genetic and rare disease info

• NIH info on Joubert syndrome with oculorenal anomalies

Joubert syndrome with oculorenal anomalies is a rare disease.