A clinical suspicion of JS may be posed in neonates presenting with hypotonia, abnormal ocular movements, delayed milestones and breathing abnormalities; yet, the confirmative diagnosis is neuroradiological, based on the detection of the MTS on brain imaging. The MTS typically arises from the combination of:
- Cerebellar vermis hypodysplasia.
- Horizontalized, thickened, and elongated superior cerebellar peduncles.
- Abnormally deep interpeduncular fossa at the level of isthmus and upper pons. All these findings create the appearance of a tooth on MRI axial images at the ponto-mesencephalic junction.
The neurologic phenotype typically includes hypotonia in infancy with later development of ataxia, developmental delay and intellectual disability of variable severity (albeit a minority of patients may have borderline cognitive defects or even be cognitively adequate). Additional common features are abnormal breathing pattern (consisting in alternating tachypnea and /or apnea) mainly in the neonatal age, which tend to spontaneously resolve with time, and aberrant eye movements (e.g. oculomotor apraxia or difficulty in smooth visual pursuit and jerkiness in gaze and tracking), strabismus and nystagmus. A minority of patients experience behavioral problems. Although several JS-causative genes can be associated with additional organ involvement (including retinopathy, cystic renal disease, nephronophthisis, hepatic fibrosis, polydactyly, and peculiar orofacial appearance), CEP120 mutations have been reported so far only in JS patients with “pure” neurological phenotypes. The diagnosis of JS can be suspected prenatally by second trimester ultrasound and confirmed by fetal MRI which can clearly show the MTS.
JATD is also diagnosed prenatally, as it is characterized by a severely constricted thorax, short stature, shortening of long bones and (inconstant) polydactyly. Among skeletal findings, cone-shaped epiphyses of hands and feet, brachydactyly, irregular metaphyses, hypoplastic iliac wings, and trident-shaped acetabular roof have been reported. Spinal abnormalities involving proximal cervical stenosis have been demonstrated in about 60% cases. Prognosis mainly depends on respiratory insufficiency that, when severe, can lead to death in the first days of life. Milder cases are at risk of developing chronic restrictive lung disease with recurrent respiratory infections. Renal cystic disease, hepatic dysfunction and retinal degeneration similar to Leber Congenital Amaurosis can also be observed.