|Year : 2020 | Volume
| Issue : 2 | Page : 108-110
Facial dysmorphism, hirsutism, and failure to thrive as manifestation of Leigh syndrome in a child with SURF1 mutation
Dhinesh Baskaran, Nahin Hussain
Department of Paediatric Neurology, Leicester Royal Infirmary, Leicester, UK
|Date of Submission||10-Sep-2018|
|Date of Decision||18-Nov-2019|
|Date of Acceptance||30-Mar-2020|
|Date of Web Publication||30-Jun-2020|
Dr. Dhinesh Baskaran
Department of Paediatric Neurology, Leicester Royal Infirmary, Leicester LE1 5WW.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Leigh syndrome (or subacute necrotizing encephalomyelopathy) is a rare neurodegenerative disorder characterized by psychomotor retardation or regression, typically occurring in stepwise decrements. Onset is typically between ages 3 and 12 months. Neurological manifestations include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy, whereas extraneurological manifestations may include hypertrophic cardiomyopathy, hypertrichosis, anemia, renal tubulopathy, liver involvement, ptosis, and muscle weakness. Approximately 50% of affected individuals die by age 3 years, most often as a result of respiratory or cardiac failure. We report a case of 22-month-old female child presenting to us with severe failure to thrive, dysmorphic features, hirsutism, external ophthalmoplegia epilepsy, and neuroregression with characteristic findings of Leigh’s syndrome on neuroimaging and her muscle biopsy revealed evidence of mitochondrial respiratory chain defect involving complex IV and SURF1 mutation.
Keywords: Leigh syndrome, mitochondrial respiratory chain, neuroregression
|How to cite this article:|
Baskaran D, Hussain N. Facial dysmorphism, hirsutism, and failure to thrive as manifestation of Leigh syndrome in a child with SURF1 mutation. J Pediatr Neurosci 2020;15:108-10
| Introduction|| |
Leigh syndrome (or subacute necrotizing encephalomyelopathy) is a rare, inherited neurodegenerative condition. It was first described by Denis Leigh (1951) in a patient with foci of necrosis and capillary proliferation in the brainstem. Mitochondrial deoxyribonucleic acid (DNA)-associated Leigh syndrome is more rare than nuclear gene-encoded Leigh syndrome, which is likely to occur in approximately 1 in 100,000 to 1 in 140,000 births. We report a case of 22-month-old female child presenting to us with epilepsy, neuroregression, and breathing abnormalities with characteristic findings of Leigh’s syndrome on neuroimaging and genetic evaluation revealed mitochondrial respiratory chain defect involving complex IV and SURF1 mutation. Leigh syndrome usually becomes apparent in infancy, often after a viral infection. Rarely, it begins in the teenage or adult years. Signs and symptoms usually progress rapidly. Neurological manifestations include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy, whereas extraneurological manifestations may include hypertrophic cardiomyopathy, hypertrichosis, anemia, renal tubulopathy, liver involvement, ptosis, and muscle weakness. Approximately 50% of affected individuals die by age 3 years, most often as a result of respiratory or cardiac failure. It occurs due to defects in genes for the pyruvate dehydrogenase complex, cytochrome-c oxidase, adenosine triphosphate synthase subunit 6, or subunits of mitochondrial complex. Patterns of inheritance include X-linked recessive, autosomal recessive, and mitochondrial.
| Case History|| |
A 22-month-old female child presented with long-standing history of severe failure to thrive, episodic muscle weakness, feeding difficulties, vomiting, and diarrhea. She was born at term gestation and her developmental milestones were unremarkable until the age of 9 months. Her investigations for failure to thrive were unremarkable, which included pH study with barium swallow, coeliac screening, small bowel, and rectal biopsy. Her height, weight, and head circumference remained below 0.4th centile. Her weight remained static in spite of different feeding and nutritional strategies, including continuous nasogastric feeding. Her exercise tolerance became progressively poor and was wheel chair bound by 20 months of age. She also had intercurrent illnesses needing antibiotics and epileptic seizures. On examination, she had dysmorphic features, hirsutism, external ophthalmoplegia, hypotonia, and ataxia. She was noticed to have intermittent sighing and labored breathing. Her blood and cerebrospinal fluid (CSF) lactate was high during one of the episodes of deterioration. Her muscle biopsy showed cytochrome C oxidase (COX) deficiency on histochemical analysis, evidence of mitochondrial respiratory chain defect involving complex IV, and SURF1 mutation. Her magnetic resonance imaging (MRI) brain [Figure 1] showed bilateral symmetric high T2 signal involving the thalamic fasciculus, red nucleus, superior cerebellar peduncles, and brain stem, which established the clinical diagnosis Leigh syndrome.
|Figure 1: MRI brain showing bilateral symmetric high T2 signal involving the thalamic fasciculus, red nucleus, and brain stem|
Click here to view
| Discussion|| |
Leigh syndrome is characterized by psychomotor retardation or regression, variably followed by transient periods of stabilization or even improvement. However, there is eventual progressive neurological decline, typically occurring in stepwise decrements with intercurrent febrile illnesses. Later onset (including in adulthood) and long-term survival may occasionally occur. Life expectancy and extra neurological manifestations appear to be related, at least in part, to the underlying genetic defect.
The following criteria have been suggested for the diagnosis of Leigh syndrome:,
Characteristic clinical presentation during infancy with neurological and extra neurological features
Bilateral symmetric T2-weighted hyperintensities in the basal ganglia and/or brain stem on brain MRI
Elevated lactate in blood and/or CSF
Either identification of pathogenic variants in a specific nuclear gene or mitochondrial deoxyribonucleic acid (mtDNA)
The term “Leigh-like syndrome” is often used when clinical and other features strongly suggest Leigh syndrome but do not fulfil the stringent diagnostic criteria. Once Leigh syndrome or a Leigh-like syndrome is considered in an individual, determining the specific cause aids in discussions of prognosis and treatment and in genetic counselling.
Although clinical findings in individuals with mutation of different genes typically overlap, there are specific clinical and/or imaging findings that guide testing of a subset of genes. For instance, SURF1 deficiency also appears to have a high incidence of hypertrichosis and peripheral neuropathy. Brain malformations are typically seen in those with mutation of PDHA1. Specific brain tracts may be involved in some subgroups of complex I deficiency; for example, brain stem lesions are seen within the mammillothalamic tracts, substantia nigra, medial lemniscus, medial longitudinal fasciculus, and spinothalamic tracts on T2-weighted MRI in individuals with mutation of NDUFAF2.
Molecular genetic testing approaches can include serial single-gene testing, use of a multi-gene panel, and more comprehensive genomic testing. Specific treatment is possible only for few specific disorders using biotin, thiamine and coenzyme Q10. In the vast majority of the cases of Leigh syndrome, management is primarily symptomatic. This includes management of acidosis by sodium bicarbonate or sodium citrate, use of antiepileptic drugs for seizures and avoidance of sodium valproate and barbiturates,, using baclofen, trihexyphenidyl or gabapentin for dystonia, surveillance for cardiomyopathy, nutritional support and psychological support. Annual or 6 monthly reviews for the patients are done to monitor progression and neurological, ophthalmological, audiological, and cardiological evaluations are recommended.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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