CEREBRAL PALSY AND GENETIC DISORDERS

Common neurodegenerative and neurometabolic disorders can be mistaken for cerebral palsy. These “CP mimickers” are now an increasingly growing group of metabolic and genetic disorderswith symptoms and signs resembling CP children. These CP mimickers are common, particularly in highly consanguineous populations. Their clinical presentation may be nonspecific or very slowly progressive, especially at the early age, hence can be easily misdiagnosed as CP. In present scenario. We are able to find out the exact aetiology by different genetic evaluation. So it is very important to identify in suspected cases where picture is not clear. Identifying the aetiology of CP has practical consequences, such as proper family counselling about the cause of the disease, risk of recurrence, prognosis, and in some diseases provide disease-modifying therapy.

Thorough history and a careful neurological examination are essential in the evaluation of a patient suspected to have CP. The increasing use of next generation sequencing in neurological, neuromuscular and metabolic conditions will detect more and more CP mimicsand therefore decreasing the total burden from CP.

The possibility of a treatable metabolic cause of CP along with a more accurate diagnosis and genetic counselling emphasizes the importance of being particularly vigilant in determining the aetiology.

When we suspect genetic cause (Cerebral Palsy Mimics) in case of child with neuro- developmental disorder?

Following are the symptoms in a patient’s history which point against the diagnosis of cerebral palsy:

Absent history of any risk factors leading to brain injury, such as prematurity, perinatal or infantile hypoxic ischemic insult, intracranial bleeding, kernicterus, cerebral vascular accident, infection, or head trauma,

Family history of CP,

Progressive neurological symptoms,

Regression of milestones,

Diurnal variation of symptoms

Fluctuation in symptoms in relation to activity or fasting,

Appears “different”/ “unusual” as compared to other family members,

Isolated motor dysfunction (hypotonia without dystonia or spasticity or isolated ataxia),

Peripheral nervous system abnormalities (sensory sign or absent reflexes),

Eye movement abnormalities (paroxysmal saccadic eye-head movements, oculogyria, or oculomotor apraxia) and

Optic atrophy or retinopathy are atypicalin CP children.

What are the investigation required to evaluate aetiology of neurodevelopmental disorder (Cerebral Palsy Mimics)

Most of the d has overlapping or non-specific phenotypes. When clinical and neuroimaging findings are non-specific and no specific cause is suspected, other investigations should be carried out to rule out an underlying metabolic or genetic disease. These investigations comprise of:

Blood investigations:

Complete blood count, liver function tests, kidney function tests, serum sodium, potassium, chloride, calcium, phosphate, ALP

Metabolic screening tests:

ABG, serum ammonia, lactate, blood glucose, urine ketones, dried blood spot for Tandem mass spectrometry (TMS), urine gas chromatography mass spectrometry (GCMS).

Biochemical tests:

Enzyme assays and functional assays

Radiological investigations:

skeletal survey, MRI brain

Electrophysiological studies:

EEG, EMG, NCV

Cytogenetic tests:

karyotyping, chromosomal microarray

Molecular tests:

PCR, Sanger sequencing, MLPA

Next-generation sequencing (whole exome sequencing/clinical exome sequencing)

In recent years, advanced genetic testing techniques have become affordable and easily available to efficiently diagnose rare disease-causing mutations in children with suspected genetic disorders.

What is the role of Genetic Clinical Specialist for evaluation of children with cerebral palsy like symptoms?

Diagnosis:

 Clinical genetics allows for the accurate diagnosis of suspected genetic disorders misdiagnosed as CP, which can be challenging based on symptoms alone.

Treatment:

Advances in clinical genetics have led to the development of personalized treatment plans for individuals with genetic disorders. These treatment plans consider the patient’s genetic mutations and other factors to optimize treatment outcomes. Surveillance protocols personalised to the child’s diagnosed condition is an aid to early detection and management of various manifestations possible.

Prevention:

Clinical genetics provides the ability to identify individuals or future offspring at increased risk of developing genetic disorders and implement preventive measures to reduce their risk. Based on the disorder identified and risk, the clinical geneticist may discuss reproductive options including prenatal diagnosis in form of Chorionic villus sampling (CVS) at 11-13weeks of pregnancy/ Amniocentesis at 16 weeks of pregnancy to test for the confirmed genetic disorder in previous sibling or family member. Option of In-vitro fertilisation (IVF) with donor egg/sperm can also be given to couples based on the disorder identified.

Research:

Clinical genetics research is critical for advancing our understanding of genetic disorders and developing new treatment options. Newer treatment options are increasingly being developed according to the specific mutation that patients carry.