Evaluation of infantile dystonia

Dystonia is a hyperkinetic movement disorder described as contraction of both agonist and antagonist muscles simultaneously, causing twisting and repetitive movements or abnormal postures.[1]Fahn S, Bressman SB, Marsden CD. Classification of dystonia. Adv Neurol. 1998;78:1-10. http://www.ncbi.nlm.nih.gov/pubmed/9750897?tool=bestpractice.com It can be confused with other abnormal movement disorders such as parkinsonism, tremor, chorea, myoclonus, tics, and stereotypies; mistaken for tonic seizures; or coexist with other features as part of a complex movement disorder. The earlier the age of onset, the more generalized and severe the condition tends to be.

The first priority in the evaluation of an infant with dystonia is to establish whether the patient has a condition needing urgent intervention. Several metabolic disorders fall into this category, so clinical biochemical tests may need to be done as part of the initial testing even if other genetic testing is being considered. See Urgent considerations.

Molecular genetic testing is important and clinically useful in infantile dystonia due to its high yield of genetic diagnoses and medically actionable information. Next-generation sequencing tests such as gene panels and exome sequencing reveal the diagnosis in up to 60% of patients with infantile-onset dystonias.[2]Wirth T, Tranchant C, Drouot N, et al. Increased diagnostic yield in complex dystonia through exome sequencing. Parkinsonism Relat Disord. 2020 May;74:50-6. http://www.ncbi.nlm.nih.gov/pubmed/32334381?tool=bestpractice.com [3]Holla VV, Neeraja K, Stezin A, et al. Utility of clinical exome sequencing in dystonia: a single-center study from India. J Mov Disord. 2022 May;15(2):156-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171311 http://www.ncbi.nlm.nih.gov/pubmed/35287262?tool=bestpractice.com ​​ However, thorough clinical evaluation beyond the dystonia itself is crucial to achieve this diagnostic rate. Phenotypic features from the history, family history, and physical exam help narrow the differential diagnosis, allow selection of the most appropriate genetic tests, and improve the interpretation of genetic testing results.

Dystonic movements

Dystonic movements are patterned and sustained. They repeatedly involve the same muscle groups. The urge to perform the dystonic movements is absent, and there is no relief after the dystonic movements are executed. Dystonia usually gets worse with fatigue and emotional stress and it gets better with sleep and relaxation.[4]Geyer HL, Bressman SB. The diagnosis of dystonia. Lancet Neurol. 2006 Sep;5(9):780-90. http://www.ncbi.nlm.nih.gov/pubmed/16914406?tool=bestpractice.com [5]Obese JA. General concepts. In: Fernández-Alvarez E, Aicardi J, eds. Movement disorders in children. London: Mac Keith Press; 2001:1-23. Photographs and video footage of affected infants are helpful in delineating the dystonic movements. Periodic follow-up is often a prerequisite to making an accurate diagnosis.

Types of infantile dystonia

In the classification of dystonias, the term infantile refers to onset from birth to 2 years of age.[6]Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729880 http://www.ncbi.nlm.nih.gov/pubmed/23649720?tool=bestpractice.com Dystonias are described according to two complementary axes:[6]Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729880 http://www.ncbi.nlm.nih.gov/pubmed/23649720?tool=bestpractice.com [7]van Egmond ME, Kuiper A, Eggink H, et al. Dystonia in children and adolescents: a systematic review and a new diagnostic algorithm. J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):774-81. https://jnnp.bmj.com/content/86/7/774.long http://www.ncbi.nlm.nih.gov/pubmed/25395479?tool=bestpractice.com

• Clinical characteristics (axis 1), which include age at onset, body distribution, temporal pattern, and associated features

• Etiology (axis 2), which includes nervous system pathology and inheritance.

Information from the history and physical examination allows an initial classification and differential diagnosis to be made. The presence and absence of motor features and other signs and symptoms can narrow the differential diagnosis by indicating a particular dystonia syndrome and by directing the diagnostic evaluation toward groups of disorders associated with different clinical patterns, such as:

• Isolated dystonia (dystonia alone or dystonia with tremor)

• Combined dystonia (dystonia with other movement disorders)

• Complex dystonia (dystonia with other symptoms).

The clinical evaluation may also indicate whether the condition is neurodegenerative or suggest an acquired or inherited etiology.

Further investigations may be required including neuroimaging, evaluation for associated neurodevelopmental or systemic abnormalities, therapeutic trial of levodopa, or biochemical (including diagnostic lumbar puncture) and genetic tests.

Several pseudodystonias need to be considered in the differential diagnosis; these conditions involve dystonia-mimicking abnormal movements, but their etiologies differ from those of dystonias.

The rapid identification of several conditions is important to prevent irreversible injury or death:

• Drug-induced acquired dystonia

• Pseudodystonia due to cervical instability

• Status dystonicus

• Multiple neurometabolic disorders, such as glutaric aciduria type I

• Acute bilirubin encephalopathy.

Many metabolic disorders present in infancy, and are high on the list of likely differential diagnoses in the first year of life.[6]Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729880 http://www.ncbi.nlm.nih.gov/pubmed/23649720?tool=bestpractice.com [8]Sanger TD. Pathophysiology of pediatric movement disorders. J Child Neurol. 2003 Sep;18 Suppl 1:S9-24. http://www.ncbi.nlm.nih.gov/pubmed/13677568?tool=bestpractice.com

Dopa-responsive dystonia (Segawa syndrome, dystonia-parkinsonism with diurnal fluctuation) needs to be considered in any infant or child with unknown diagnosis and normal magnetic resonance imaging. It is usually misdiagnosed as spastic diplegic or quadriplegic cerebral palsy, intractable epilepsy, or hereditary spastic paraplegia.[9]Kamal N, Bhat DP, Carrick E. Dopa-responsive dystonia (Segawa syndrome). Indian Pediatr. 2006 Jul;43(7):635-8. http://www.indianpediatrics.net/july2006/635.pdf http://www.ncbi.nlm.nih.gov/pubmed/16891685?tool=bestpractice.com [10]Jan MM. Misdiagnosis in children with dopa-responsive dystonia. Pediatr Neurol. 2004 Oct;31(4):298-303. http://www.ncbi.nlm.nih.gov/pubmed/15464646?tool=bestpractice.com