Joubert syndrome: long‐term follow‐up

Abstract

Twenty-nine patients (16 males, 13 females) with Joubert syndrome were identified from ophthalmology, neurology, and genetic databases covering a 15-year period at Great Ormond Street Hospital, London. Criteria for diagnosis included absent or markedly hypoplastic cerebellar vermis, abnormal eye movements, and developmental delay. Five patients had died. Scans and notes were available for 22 patients, and 18 cases were clinically reviewed. The median age was 10 years 10 months (range 3mo to 19y) and the median follow-up was 8 years 5 months (range 3mo to 19y, with one new patient seen at 3mo of age). Cerebellar vermis hypoplasia/aplasia with 'molar tooth sign' in the axial plane was present in 22 of 22 patients, coloboma in 6 of 22, and polydactyly in 6 of 22. In the 18 clinically reviewed, apnoea occurred in 13 patients. Five had renal problems with cysts and 4 of 5 had abnormal electroretinograms (ERGs). Visual electrophysiology was abnormal in 14 of 18 patients, and in 6 there was evidence of deterioration in the ERG. Blood investigations of organic acids, phytanic acid, very-long-chain fatty acid, and transferrin were normal in 12 patients tested. Developmental assessment showed that 6 of 15 patients aged more than 5 years were at mainstream school, and 12 of 18 had started walking between 22 months and 10 years. Speech difficulties and behavioural problems were prominent.

Ophthalmological findings in Joubert syndrome

“…6,[8][9][10] Four of our patients had such findings. Genotype-phenotype correlations have emphasized the predictive value of specific mutations for retinal involvement.…”

“…Our findings of ocular motor defects are in agreement with the findings of earlier studies. 4,7,9,10 Defects in smooth pursuit and VOR cancellation can be contributed to deformed cerebellar vermis. Saccades and quick phases of nystagmus are generated involving the brainstem.…”

“…5 Ocular and oculomotor involvement is common in JS. 4,[6][7][8][9][10] However, findings differ considerably because of a wide range of phenotypic variability among patients with JS.…”

Expanding the molecular basis and phenotypic spectrum of X-linked Joubert syndrome associated with OFD1 mutations

“…6 The extended anomalies seen in this family include polycystic kidney disease, hydrocephalus, polymicrogyria and possibly congenital heart disease. Hydrocephalus is reported in a minority of females with OFD1, as is cerebellar hypoplasia and Dandy Walker malformation, 7,8 but the spectrum of anomalies can extend to cerebral dysgenesis with evidence of a severe neuronal migration abnormality in one female fetus.…”

Developmental abnormalities of the optic nerve and chiasm

“…Up to a quarter have colobomas. 22 Branchio-oculofacial syndrome The branchio-oculofacial syndrome is an autosomal dominant syndrome with variable expression. Patients have hypertrophy of the lateral pillars of the philtrum, which may look like a poorly repaired cleft lip, prominent and bilateral, vertical ridges between the lip and the nose, and aplastic or haemangiomatous cervical skin lesions, which may contain thymic tissue, with or without branchial sinuses.…”