Background: Described in 2014, Poretti–Boltshauser syndrome (PTBHS) combines delayed motor development, DI, oculomotor apraxia, severe myopia and cerebellar dysplasia with cysts. This disorder is linked to recessive mutations of CO01 gene that codes one of the subunits of laminins, a major protein component of the basal membrane.
Methods: We describe ten unrelated patients with cerebellar dysplasia, initially referred for Joubert syndrome or dystroglycanopathy due to the presence of cerebellar cysts, in whom we identified biallelic CO01 mutations by NGS.
Results: At the last follow-up, these children were between the ages of 3, 7, and 18 years. The first symptoms were noticed before the age of 4 months. These infants appeared visually impaired with poor visual fixation and pursuit and had hypotonia. Ocular motor apraxia became obvious in nine patients once they achieved head control and abnormal smooth tracking was report in the last patient. All had a delay in motor acquisitions with a nonprogressive ataxia (autonomous walking acquired between 18–48 months). Myopia was present in nine patients, severe in five. Nystagmus (2), strabismus (4), retinal abnormalities (2) and optic atrophy (2) were also noticed. In addition to these previously reported clinicoradiological characteristics, we observed new features in these patients. Two patients had hydrocephalus and one severe ventriculomegaly; one patient had an occipital cephalocele and one an occipital cutis aplasia suggesting a cranial dysraphism; and four of them had a dysmorphic tectum. Moreover, prenatal ultrasonography detected a ventriculomegaly in three patients with an abnormal cerebellar vermis in one, while until now no prenatal abnormalities were reported in PTBHS. It is important to underline, that IQ was in normal range but heterogeneous in three patients and that nine children were attending normal school with rehabilitation and one special school for visually impaired children.
Conclusion: Our findings enlarge the spectrum of structural defects due to biallelic CO01 mutations. Interestingly, as cerebellar cysts, hydrocephalus, tectal dysplasia and occipital cephalocele are reported in dystroglycanopathies and in children with other laminins mutations (LAMB1, LAMC1, and LAMB2). In addition, prenatal ultrasonography may detect ventriculomegaly and cerebellar dysplasia in these patients, but not cerebellar cysts. Concerning prognosis, all of these patients acquired autonomous walking, despite cognitive difficulties they can most often be schooled normally, even if some are visually impaired.
