Objective: To describe a case of NKX2-1 mutation presenting with nocturnal hyperkinetic movements.

Background: NKX-2-1 mutation is associated with benign hereditary chorea, respiratory distress in neonates, and hypothyroidism (brain-lung-thyroid syndrome) [1]. ACDY5 mutation can also present with childhood-onset chorea, and is characteristically associated with episodic hyperkinetic movements such as dystonia during sleep. Both have an autosomal dominant inheritance pattern. Here we describe a case of NKX2-1 mutation with hyperkinetic/dystonic movements in sleep.

Methods: We present the case of a 10 year old boy presenting with chorea since infancy and violent contortions of his legs at night while sleeping or drowsy. His was born at thirty-six week gestation and required CPAP and steroids for premature lungs. His neurodevelopmental history was notable for sitting unsupported at 17 months, walking a few steps at age 2, with independent walking at age 3.5. He commenced reading at age 8. Family history was notable for an autosomal dominant pattern of father, grandfather, and aunt requiring braces. His father had hyperkinetic movements “he outgrew”, but details were limited. On examination he had choreiform movements of all extremities and face, exacerbated with movement/running. There was no ataxia, peripheral neuropathy or spasticity.

Results: CSF and Brain imaging was non-diagnostic. Genetic testing revealed a 271.47 kb deletion in the NKX2-1 gene, and ADCY-5 testing was negative.

Conclusions: In the literature, violent dyskinesias in stages of sleep and drowsiness has been described as characteristic of an ADCY5 mutations, and not in NKX2-1 deletions. [2] Our patient also had motor/language milestone delay and axial hypotonia (during infancy only) which has been reported more frequently in ADCY5 mutations [2]. He did have a history of subclinical hypothyroidism and respiratory distress syndrome in infancy, fitting with other well known medical issues reported in NKX2-1 [1]. When developing a differential diagnosis, it is important to consider that nocturnal dyskinesias may be related to NKX2-1 rather than ADCY5 mutations.

References: [1] Gras D, Jonard L, Roze E, et al. Benign hereditary chorea: phenotype, prognosis, therapeutic outcome and long term follow-up in a large series with new mutations in the TITF1/NKX2-1 gene. Neurol Neurosurg Psychiatry 2012; 83: 956-962. [2] Mencacci N, Erro R, et al. ADCY5 mutations are another cause of benign hereditary chorea. Neurology 2015; 85:80-88.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/benign-hereditary-chorea-with-nocturnal-dyskinesias/