Nystagmus in a newborn: a manifestation of Joubert syndrome in the neonatal period

Abstract

Joubert syndrome is a rare disorder, usually autosomal recessive, with a prevalence of 1:80 000 to 1:100 000. This disease presents most commonly as breathing irregularities, although the two major clinical criteria are hypotonia and developmental delay, sometimes associated with ocular movement abnormalities. The severity of the presentation varies, ranging from mild cases with normal intelligence to severe developmental delays associated with early death. We report a case of a newborn who presented to the emergency department for absent ocular fixation and torsional nystagmus without other neurological abnormalities. Her cranial MR showed cerebellar vermis agenesis and a molar tooth sign. Her laboratory evaluation, and renal and abdominal ultrasound were normal. An electroretinogram showed mixed retinal dystrophy and an AHI1 homozygous missense c.1981T>C mutation was identified (parents are carriers). Throughout infancy, she has shown mild developmental delay and hypotonia, but no respiratory abnormalities. Owing to variable expressivity, a high level of suspicion is required.

Review of Ocular Manifestations of Joubert Syndrome

“…Abnormal eye movements, including primary position nystagmus, are a common feature in JS [11,14,43,57,65,67,72,73,77,79,84,85,86,87,90,94,95,96,97,98,99,100,101,102,103,104,105]. Fluxes in gaze holding, an early symptom, were described in a study of six patients with JS.…”

Loss of the neurodevelopmental Joubert syndrome causing protein, Ahi1, causes motor and muscle development delays independent of central nervous system involvement

“…No effect on gross brain morphology in Ahi1 −/− mice Due to known abnormal gross cerebellar morphology, which frequently occurs in humans with AHI1 mutations (Chafai-Elalaoui et al, 2015;Ferland et al, 2004;Salva et al, 2016;Valente et al, 2006), as well as previously reported reductions in brain and cerebellar size in Ahi1 −/− mice bred on a 129/SvJ/C57BL/6 genetic background (Lancaster et al, 2011), we performed analyses of total brain and cerebellar size in our Ahi1 −/− mice. No gross anomalies in brain morphology were identified in 10-week old male Ahi1 −/− mice on midsagittal sections (Fig.…”

Nadir Bir Siliopati: Joubert Sendromu

“…Joubert Sendromuna yol açan 40'a yakın gen literatürde tanımlanmıştır ve vakaların ancak %50'sinde genetik kusur bulunabilmiştir. NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, MKS3, ARL13B ve CC2D2A gibi genlerin patogenezde nedensel bir rol oynadığı bilinmektedir (7,8). Hastamıza yapılan mikrodizin analizinde tüm tanımlı genlerin homozigot delesyonları dışlanmıştır.…”