Horizontal gaze palsy with progressive scoliosis: CT and MR findings

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital disorder characterized by absence of conjugate horizontal eye movements and progressive scoliosis developing in childhood and adolescence. We present a child with clinical and neuroimaging findings typical of HGPPS. CT and MRI of the brain demonstrated pons hypoplasia, absence of the facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft. We briefly discuss the imaging aspects of this rare entity in light of the current literature.     

Congenital ocular motor apraxia. Case reports and literature review

Two children with congenital ocular motor apraxia (C-OMA) associated with congenital malformations of the central nervous system (CNS) are presented, and the literature is reviewed. C-OMA is an abnormality of ocular motility characterized by defective or absent voluntary horizontal gaze, associated with a characteristic head thrust. Although not rare, it is infrequently recognized. C-OMA is not a specific disease entity, but a sign. It may be associated with other static congenital CNS disorders and must be distinguished from acquired ocular motor apraxias (A-OMA) seen in progressive brain disorders and in certain serious systemic diseases. Therefore, when movements typical of C-OMA are observed, a careful systemic and neurologic examination should be performed, including immunoglobulin screening, cranial computerized tomography scanning, and adequate follow-up. Close relatives also should be examined.     

Unilateral blepharoptosis with synkinetic movements of the eyelids on horizontal gaze

A 17-year-old woman with a left congenital ptosis and an alternating esotropia is presented. During horizontal gaze to the right and left, the eyelid of the abducting eye elevated and the eyelid of the adducting eye lowered. There were no synkinetic eyelid movements with contraction of the pterygoid, sternocleidomastoid, or facial muscles. Synkinetic eyelid movements due to aberrant regeneration were unlikely due to absence of previous third nerve palsy. A supranuclear innervational abnormality is proposed to explain the clinical findings.     

Pontine cavernous hemangioma presenting with horizontal gaze palsy

Pontine cavernous hemangioma presenting as horizontal gaze palsy is extremely rare. A 32-years-old patient presented with left horizontal gaze palsy with left esotropia. A large pontine mass was present which was removed in-toto using a sub-occipital craniotomy. Post- operatively, the gaze palsy showed recovery and the diplopia decreased. Follow-up MRI showed no residual mass.     

Pelizaeus–Merzbacher Disease: the First Genetically Approved Case Report from Iran

Background

Classic Pelizaeus-Merzbacher disease is a rare x-linked disorder of proteolipid protein expression first described clinically in 1885. This disease is characterized by abnormal eye movements, very slow motor development and involuntary movements. The causative gene is PLP1.

Case Presentation

A 1-year-old boy was referred to our clinic due to abnormal eye movements. He had horizontal and flickering eye oscillation, psychomotor retardation, hypotonia and head nodding. We found hypomyelination in brain MRI.

Conclusion

The possibility of Pelizaeus-Merzbacher disease should be considered in boys with abnormal eye movements, psychomotor retardation and hypotonia.     

Scoliosis and lateral gaze paralysis. Description of a case and review of the literature

The paper reports the case of a girl affected by progressive scoliosis and paralysis of the horizontal gaze, and reviews previously published cases. This is a rare and little known neurological entity transmitted by recessive autosomal inheritance. To all effects, this appears to be the first report of an Italian case. A correct early diagnosis is of considerable importance in view of appropriate genetic counselling.     

Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis

Congenital ocular motor apraxia type Cogan is characterized by impairment of horizontal voluntary eye movements, ocular attraction movements, and optokinetic nystagmus. Two patients with congenital ocular motor apraxia type Cogan exhibited a newly recognized association with nephronophthisis type 1, an autosomal recessive kidney disease. Both patients possess large deletions of the NPHP1 gene. The deletion occurred on both chromosomes 2q13 in one patient and heterozygously in combination with a point mutation of the NPHP1 gene in the other. The findings will help to elucidate the pathogenetic processes involved.     

Clinicoradiological correlation of scoliosis in children with Jarcho-Levin and Escobar syndromes: associated “flat bone or wing-like” imaging findings

Congenital or early onset scoliosis may be the lead clinical feature in several rare syndromes. In this paper, we present the imaging findings in two children with early onset scoliosis related to the Jarcho-Levin and Escobar syndromes and an osseous plate or wing-like bar extending along the posterior elements of the spine on computed tomography. The clinical phenotypes in these syndromes are variable. A thorough clinical evaluation with imaging correlation is essential. The recognition of underlying spinal anomalies is essential in planning treatment and estimating prognosis. In young children with progressive scoliosis, cross-sectional imaging plays a major role in the diagnostic work-up. Conclusion: Congenital scoliosis requires a comprehensive clinical evaluation and imaging work-up. The presence of an osseous plate or wing-like fusion of posterior elements of the spine may suggest the diagnosis of Jarcho-Levin and Escobar syndromes.     

Locked-in syndrome: A rare manifestation of pediatric stroke

Locked-in syndrome is characterized by upper motor neuron quadriplegia, paralysis of lower cranial nerves, bilateral horizontal gaze palsy and anarthria, with preserved consciousness. It is due to a ventral pontine lesion following a basilar artery occlusion. We report the first Indian case report of locked-in syndrome, a 10-year old girl in whom the syndome was preceded by a ‘herald hemiparesis’. Although the exact etiology for the basilar artery occlusion could not be determined, treatment with low molecular weight heparin and warfarin was followed by partial recovery.     

Central core disease: clinical, pathological, and genetic features

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.     

Central core disease: clinical, pathological, and genetic features.

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.     

Marinesco-Sjögren syndrome due to SIL1 mutations with a comment on the clinical phenotype

BackgroundMarinesco-Sjögren syndrome is an autosomal recessive cerebellar ataxia, characterised by cerebellar ataxia, myopathy, cataracts and intellectual disability, due to mutations in the SIL1 gene.MethodsThe clinical features and two novel SIL1 mutations of four Dutch patients with Marinesco-Sjögren syndrome are described and compared to the literature on genetically proven Marinesco-Sjögren patients.ResultsThe core phenotype of this syndrome appears homogeneous, but: [1] cataract can develop later than the motor and cognitive signs; [2] myopathy is an early feature that seems progressive during the course of the disease; [3] serum creatine kinase is normal or only mildly elevated; [4] peripheral neuropathy is absent; and [5] a variable degree of intellectual disability is present in most Marinesco-Sjögren patients.ConclusionsBecause the late appearance of some hallmarks and the uncertainty as to whether incomplete phenotypes occur, SIL1 mutation analysis is helpful early in the diagnostic work-up of children with suspected inherited ataxias.     

Development of smooth pursuit eye movements in very prematurely born infants: 2. The low-risk subgroup

Aim: To investigate the impact of premature birth on visual tracking in a group of 37 infants, born before the 32nd gestational weeks (mean 29 + 6 weeks) and diagnosed as being without major neonatal complications. This paper is a part of the LOVIS study (Strand Brodd, Ewald, Grönqvist, Holmström, Strömberg, Von Hofsten, et al. Acta Pediatrica, 2011). Methods: At 2 and 4 months corrected age, eye and head movements were measured when the infant tracked a moving object. The eye movements were analysed in terms of smooth pursuit and saccades (Vision Res, 37, 1997, 1799; Exp Brain Res, 146, 2002, 257). Accuracy of gaze, proportion of smooth pursuit, head movements and saccades were calculated. Results: Between 2 and 4 months of age, all infants improved their ability to smoothly pursue a moving object. However, at both occasions, the preterm infants had less proportion smooth pursuit than the full‐term infants. The groups did not differ with respect to gaze and head movements, but the saccade frequency was higher for the very preterms in some of the conditions. Conclusion: The development of smooth pursuit in the low‐risk preterm infant group was strongly delayed compared to typically developed infants. Thus, the 2 months or more extra visual experience did not have a distinguishable positive effect on visuo‐motor development as expressed in smooth pursuit.     

Isolated unilateral gaze palsy

A case of an isolated unilateral horizontal gaze paralysis is presented. The abnormality has remained static and in isolation for more than three years. A review of the benign causes of pontine gaze palsies is presented. The unique features of this case is the fact that the gaze paralysis is unilateral and unassociated with any other neurologic or systemic abnormality.     

Ocular motor apraxia associated with intracranial lipoma

Congenital ocular motor apraxia is rarely associated with brain tumors. A 10-month-old girl with normal vertical eye movements and head thrusting to initiate horizontal saccades is presented. CT brain scan revealed a midline posterior fossa mass and histopathology confirmed the clinical diagnosis of lipoma. Unlike previously described cases of posterior fossa brain tumors associated with congenital ocular motor apraxia, this patient showed persistent ocular motor apraxia despite complete resection of the tumor.     

Expanding phenotype of mitochondrial depletion syndrome in association with TWNK mutations

Mitochondrial DNA depletion syndromes (MDS) are a group of clinically and genetically heterogeneous autosomal recessive disorders characterized by a reduction of mtDNA. We report two siblings of Armenian origin with early onset neurodegenerative disease characterized by encephalopathy, severe hypotonia, facial dyskinetic movements, abnormal eye movements, severe failure to thrive, and abnormal renal and hepatic function. Sanger sequencing confirmed two variants in the C10orf2 gene (TWNK) and indicated a diagnosis of MDS. Our recent observation confirms that nephrocalcinosis and proximal tubulopathy can be a part of a clinical picture of MDS associated with TWNK mutations and document peculiar ocular and orobuccolingual dyskinesias. Wrist myoclonia and tongue tremor were new clinical features in our patients. We suggest that the above-mentioned clinical constellation could potentially provide the basis for the diagnosis of MDS.     

Development of smooth pursuit eye movements in very preterm infants: 1. General aspects

Aim: To investigate early oculo‐motor development in a population‐based cohort of very preterm infants. Methods: Early oculo‐motor development was prospectively studied by measuring smooth pursuit eye movements at 2 and 4 months corrected age in a population of very preterm infants born in Uppsala County 2004–2007. Eighty‐one preterm infants were studied, and 32 healthy term infants constituted the control group. Results: The study group consisted of infants with a mean gestational age of 28 + 5 weeks. At 2 and 4 months corrected age, infants born very preterm showed lower gain (p < 0.001) and proportion of smooth pursuit eye movements (p < 0.001) compared to the control group. The boys showed higher gain of smooth pursuit eye movements at both 2 and 4 months corrected age, compared to girls. Conclusions: Oculo‐motor development measured by smooth pursuit eye movements is delayed in very preterm infants at 2 and 4 months corrected age. This might be a risk factor or early indicator of later perceptual and behavioural impairment.     

Communication ability in cerebral palsy: A study from the CP register of western Sweden

BackgroundCommunication is often impaired in cerebral palsy (CP). Tools are needed to describe this complex function, in order to provide effective support.AimTo study communication ability and the relationship between the Communication Function Classification System (CFCS) and CP subtype, gross motor function, manual ability, cognitive function and neuroimaging findings in the CP register of western Sweden.MethodsSixty-eight children (29 girls), 14 with unilateral spastic CP, 35 with bilateral spastic CP and 19 with dyskinetic CP, participated. The CFCS, Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) levels, cognitive impairment and neuroimaging findings were recorded.ResultsHalf the children used speech, 32% used communication boards/books and 16% relied on body movements, eye gaze and sounds. Twenty-eight per cent were at the most functional CFCS level I, 13% at level II, 21% at level III, 10% at level IV and 28% at level V. CFCS levels I–II were found in 71% of children with unilateral spastic CP, 46% in bilateral spastic CP and 11% in dyskinetic CP (p = 0.03). CFCS correlated with the GMFCS, MACS and cognitive function (p < 0.01). Periventricular lesions were associated with speech and more functional CFCS levels, while cortical/subcortical and basal ganglia lesions were associated with the absence of speech and less functional CFCS levels (p < 0.01).ConclusionCommunication function profiles in CP can be derived from the CFCS, which correlates to gross and fine motor and cognitive function. Good communication ability is associated with lesions acquired early, rather than late, in the third trimester.     

Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism

We report a novel inborn error of metabolism identified in a child with an unusual neurodegenerative disease. The male patient was born at term and recovered well from a postnatal episode of metabolic decompensation and lactic acidosis. Psychomotor development in the first year of life was only moderately delayed. After 14 mo of age, there was progressive loss of mental and motor skills; at 2 years of age, he was severely retarded with marked restlessness, choreoathetoid movements, absence of directed hand movements, marked hypotonia and little reaction to external stimuli. Notable laboratory findings included marked elevations of urinary 2-methyl-3-hydroxybutyrate and tiglylglycine without elevation of 2-methylacetoacetate, mild elevations of lactate in CSF and blood, and a slightly abnormal acylcarnitine profile. These abnormalities became more apparent after isoleucine challenge. Enzyme studies showed absent activity of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in the mitochondrial oxidation of 2-methyl branched-chain fatty acids and isoleucine. Under dietary isoleucine restriction, neurologic symptoms stabilized over the next 7 months.     

Alexander Disease: Report of Two Unrelated Infantile Form Cases,Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran

Background

Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia. The diagnosis is based on magnetic resonance imaging (MRI) findings and confirmed by GFAP gene molecular testing. GFAP gene encodes glial fibrillary acidic protein, is the only gene in which mutation is currently known to cause AD which is inherited in autosomal dominant manner.

Case Presentation

In this article we report the first two Iranian cases of infantile AD and their clinical, brain MRI and molecular findings. We report two novel mutations too in the GFAP gene that are associated with infantile form of AD.

Conclusion

GFAP gene mutations are a reliable marker for infantile AD diagnosed according to clinical and MRI defined criteria. A genotype-phenotype correlation had been discerned for the two most frequently reported GFAP gene mutations in infantile type of AD (R79 and R239), with the phenotype of the R79 mutations appearing much less severe than that of the R239 mutations. Our findings confirm this theory.