Dr.Sruthi Suresh, Dr.Sajitha Nair, Dr.Vaishak (Pediatric neurology), Dr.C.Jayakumar
AIMS, Kochi
One year 8 month old child, 1st of non-consanguineous marriage presented with delayed attainment of developmental milestones.
She was born preterm at 32 weeks -Emergency LSCS – in view of peripartum haemorrhage and circulatory shock -with delayed perinatal transition requiring prolonged NICU stay due to respiratory distress -mechanically ventilation for 2 days and CPAP for 2 weeks).Neuro sonogram at birth revealed grade one Intra ventricular haemorrhage . Outside hospital MRI brain revealed bilateral small posterior peri-ventricular white matter hyperintensities, suggestive of sequel of old hypoxic insult. She was thus brought for further evaluation and management.
Immunised for age according to NIS.
Recurrent admissions since 7 months of life, in view of LRTI 2-3 episodes/ month)
Was evaluated for tuberculosis which was negative.
CT chest done in October 2023 showed complete collapse of right lower lobe with compensatory hyperinflation of upper and middle lobe – ?chronic collapse secondary to aspiration.
CT pulmonary angiogram was done which showed no abnormal systemic arterial supply or venous drainage.
Barium meal done in January, 2024 showed Grade 1 gastro oesophageal reflux.
ECHO was done in view of recurrent lower respiratory tract infections which was normal. In view of choking and coughing while feeding, swallow study was done which showed she was fit for oral feeds.
Developmental Milestones:
1. Gross motor- Neck control at 7 months, rolling over 7 months, sitting with support- not attained.
2. Fine motor- Bidextrous grasp at 8 months, transfer objects to other hand at 9 months, immature pincer at 1 year of age
3. Language – Cooing at 9-10 months, babbling 11 months, monosyllables at 1 year, bisyllables 1.5 years. Now can speak around 4-5 words.
4. Social: Social smile at 8 months ,recognised mother at 8 months, stranger anxiety 9 months. Does not wave e e.
On examination: Alert, playful. Vitals stable but respiratory rate vary between 30-60/minute
AUXOLOGY
Weight: 9.8 kg (25th centile)
Height :73 cms (< 3rd centile)
Head circumference :46cm (25th-50th centile).
US :LS ratio 1.2.
Extensive hyperpigmented plaque over the medial surface of right thigh.
Dolicocephaly noted with coarse facies. Frontal bossing with low set ears and short neck.
Oculomotor apraxia+.
CNS examination :
Cranial nerves
Active Pupils- both eyes reacting equally to light.
Axial and appendicular hypotonia. Observed power more than 3/5.Deep Tendon Reflexes: 2+ in all 4 limbs.
The overall clinical profile was suggestive of global developmental delay with oculomotor apraxia/ Joubert spectrum disorder.
Routine blood investigationsdone were normal.
MRI Brain showed thick, horizontally oriented superior cerebellar peduncles with deep interpeduncular fossa giving a molar tooth appearance.
Dysplastic superior vermis with folial pattern abnormalities were also noted.
Hence, a probable diagnosis of Joubert syndrome was made.
MRI brain showing Molar tooth sign
Visual Evoked Potential (VEP) and Brainstem Auditory Evoked Potential (BAEP) were normal. USG abdomen showed borderline hepatomegaly. Ophthalmology consultation was sought, fundus was normal. Whole exome sequencing was sent which reported as Joubert syndrome.
Developmental therapy was initiated and planned for a PEG insertion in view of recurrent aspiration pneumonias.
Joubert syndrome is a rare autosomal recessive ciliopathy characterized cerebellar vermis hypoplasia, often presenting with the distinctive “molar tooth sign” on axial MRI. Clinically, it manifests with hypotonia, ataxia, oculomotor apraxia, and developmental delays. Additional features may include episodic tachypnea, renal cystic disease, and retinal dystrophy, contributing to a multisystem involvement. The syndrome exhibits genetic heterogeneity, with pathogenic variants identified in more than 30 genes, notably including AHI1, CEP290, and TMEM67. Early identification through neuroimaging and genetic testing is essential for prognostic evaluation and genetic counselling. Management requires a multidisciplinary approach, addressing neurodevelopmental needs and monitoring for potential complications such as nephronophthisis and retinal degeneration.