<i>TBC1D2B</i> -related Neurodevelopmental Disorder with Gingival Overgrowth and Movement Disorders: A Case Series and Literature Review

Recent studies have identified biallelic loss-of-function variants in the TBC1D2B gene, [1][2][3] giving rise to a combination of neurodevelopmental and neurodegenerative traits, associated with distinctive facial and gingival overgrowth. 4We report three new patients with TBC1D2B variants, expanding the phenotypic spectrum. Case series Case 1A 22-year-old female, first-born of non-consanguineous parents, was delivered vaginally with normal development milestones.At the age of 5, she was operated for a posterior subcapsular cataract in the left eye.At 12, she developed progressive imbalance while walking.At age 14, she had progressive dysarthria and developed facial freckling.At age 17, she developed progressive hand tremors.On examination, she had facial freckles, coarse facies with a broad nasal bridge, pigmentary retinopathy and gingival overgrowth (Figure 1).Neurological examination revealed scanning speech, macro-saccadic oscillations, gaze evoked nystagmus, brisk reflexes, impaired finger-to-nose test, dysdiadochokinesia, impaired heel-to-shin test, bilateral upper limb dystonic tremors and ataxic gait (Video 1). Case 2Case 1's younger brother was born at term by vaginal delivery and had normal developmental milestones.He developed generalized seizures at age 5 years, for which he was started on valproic acid.He remained seizure-free for two years, following which the drug was tapered and discontinued, without further seizure recurrence.From 10 years of age, he developed mild gait instability.Physical examination at 20 years revealed coarse facies and gingival overgrowth (Figure 1).Neurological examination revealed hypometric saccades, broken pursuits, mild gait ataxia and brisk reflexes (Video 2).