Elsevier

Pediatric Neurology

Volume 34, Issue 6, June 2006, Pages 486-489
Pediatric Neurology

Case report
Facial Dysmorphism in Leigh Syndrome With SURF-1 Mutation and COX Deficiency

https://doi.org/10.1016/j.pediatrneurol.2005.10.020Get rights and content

Leigh syndrome is an inherited, progressive neurodegenerative disorder of infancy and childhood. Mutations in the nuclear SURF-1 gene are specifically associated with cytochrome C oxidase–deficient Leigh syndrome. This report describes two patients with similar facial features. One of them was a 2½-year-old male, and the other was a 3-year-old male with a mutation in SURF-1 gene and facial dysmorphism including frontal bossing, brachycephaly, hypertrichosis, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, hypertrophic gums, irregularly placed teeth, upturned nostril, low-set big ears, and retrognathi. The first patient’s magnetic resonance imaging at 15 months of age indicated mild symmetric T2 prolongation involving the subthalamic nuclei. His second magnetic resonance imaging at 2 years old revealed a symmetric T2 prolongation involving the subthalamic nuclei, substantia nigra, and medulla lesions. In the second child, at the age of 2 the first magnetic resonance imaging documented heavy brainstem and subthalamic nuclei involvement. A second magnetic resonance imaging, performed when he was 3 years old, revealed diffuse involvement of the substantia nigra and hyperintense lesions of the central tegmental tract in addition to previous lesions. Facial dysmorphism and magnetic resonance imaging findings, observed in these cases, can be specific findings in Leigh syndrome patients with cytochrome C oxidase deficiency. SURF-1 gene mutations must be particularly reviewed in such patients. şil G, Köksal V. Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency.

Introduction

Leigh syndrome, or subacute necrotizing encephalomyelopathy, is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord [1]. Clinical symptoms depend on which areas of the central nervous system are involved.

Clinical features usually emerge in the first few years of life. Hypotonia, failure to thrive, psychomotor regression, ataxia, ocular movement abnormalities, dystonia, swallowing, and respiratory disturbances are the most commonly observed findings [2].

The most common underlying cause is a defect in oxidative phosphorylation. Genetic heterogeneity has been confirmed with the identification of functional or molecular defects in several enzyme systems involved in mitochondrial energy production, including the pyruvate dehydrogenase complex, respiratory chain complexes I-IV (cytochrome C oxidase), and the mitochondria-encoded adenosine triphosphatase 6 subunit of complex V [3], [4]. An isolated, generalized defect of cytochrome C oxidase is one of the most common biochemical abnormalities evident in patients with Leigh syndrome. Human cytochrome C oxidase is composed of 13 subunits, of which three are encoded by mitochondrial deoxyribonucleic acid and the remainder by nuclear deoxyribonucleic acid. Loss of function mutation of one of these nuclear genes, SURF-1, is specifically associated with cytochrome C oxidase–deficient Leigh syndrome [4], [5], [6], [7].

Many investigators have discussed the imaging findings in Leigh syndrome and have tried to correlate a specific enzyme defect to a homogeneous radiologic pattern. This report discusses the relationship between clinical and imaging findings in Leigh syndrome with specific enzyme and gene defects.

Section snippets

Case Report

A 3-year-old male presented with psychomotor regression, developmental delay, and failure to thrive. The neonatal period was unremarkable. At 4 months of age, he was able to roll around and hold his head. He sat at the first year and talked in simple sentences at 2 years of age. At 13 months, his developmental milestones slowed and muscle hypotonia appeared. At 18 months he manifested neurodevelopmental regression, generalized hypotonia, respiratory problems, and absent deep tendon reflexes.

On

Discussion

Several magnetic resonance image findings of Leigh disease have been reported to date. Typical imaging findings have been considered as a diagnostic hallmark [8], [9]. Bilateral putaminal lesions have long been considered a consistent feature of Leigh syndrome on magnetic resonance imaging studies; however, the magnetic resonance imaging picture may include the medulla, substantia nigra, cerebral peduncles, decussation of superior cerebellar peduncles, brachium of inferior colliculi,

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    Dysmorphic findings have been previously reported in a small number of studies. Sonam et al. described triangular face and low-set ear similar to our patients [28,31,32,40]. Although dysmorphological findings in such a large group have not been described so far, we have not observed the same prototype in all our patients.

  • Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations

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    Cutaneous and hair abnormalities have been previously reported in children with mitochondrial respiratory chain disorders [16]. Hypertrichosis has been frequently reported in Leigh syndrome due to SURF1 mutation [9–11,17–20]. It is noteworthy that in addition to the hypertrichosis noted in all patients one patient also had heterochromia of the iris and diffuse hypopigmentation.

  • Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations

    2012, Brain and Development
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    Our two cases presented with mental retardation, failure to thrive, respiratory dysfunction, facial dysmorphism and hypertrichosis. Facial dysmorphism including micrognathia and hypertrichosis especially in the extremities have been reported to be distinctive and characteristic feature of SURF1 gene mutation [3,4]. Our two cases underscore the importance of SURF1 analysis in Leigh syndrome with facial dysmorphism and hypertrichosis.

  • High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients

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    In most cases significant reduction of COX activity to 10–25% of the lowest control values was observed in all tissues.9–12 To date, about 60 different mutations in the SURF1 gene have been identified in approximately 90 LS patients.9–42 Among many various deleterious mutations occurring in single families, there are two recurrent changes found in unrelated patients from different populations, c.845_846delCT and c.311_312insAT312_321del10.

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