Clinical and magnetic resonance imaging features of elderly onset dentatorubral–pallidoluysian atrophy

Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar ataxia caused by CAG triplet expansion in atrophin 1 and is frequently associated with cerebral white matter lesions. To elucidate the clinical features of elderly onset DRPLA and the key radiological findings for differentiating DRPLA from physiological white matter lesions in healthy elderly subjects, we reviewed the clinical and magnetic resonance imaging (MRI) features of ten patients with elderly onset genetically confirmed DRPLA (> 60 years) and compared their MRI findings with those of age- and sex-matched ten healthy subjects with asymptomatic cerebral white matter lesions. The initial symptom was cerebellar ataxia in all DRPLA patients, and five of them did not have any symptoms other than ataxia at the time of MRI examination. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum was detected in all DRPLA patients and none of the healthy subjects. Abnormal signals in the brainstem (inferior olive, pons, and midbrain), thalamus, and cerebellar white matter were frequently observed in elderly onset DRPLA patients but not in healthy subjects. In conclusion, elderly onset DRPLA presents as cerebellar ataxia alone in the early stage of disease. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum and abnormal signals in the brainstem, cerebellum, and thalamus are key findings for differentiating elderly onset DRPLA from asymptomatic cerebral white matter lesions in healthy subjects.     

Migraine with aura and white matter lesions: an MRI study

Several studies report the presence of white matter lesions on brain magnetic resonance imaging in patients with migraine. The aim of our study was to detect the entity of white matter T2-hyperintensities in 90 high selected patients affected by migraine with aura, compared to a group of 90 healthy controls. We found no significant difference of incidence of white matter alterations comparing these two groups.     

A novel de novo TMEM63A variant in a patient with severe hypomyelination and global developmental delay

BackgroundHeterozygous variants in TMEM63A have been recently identified as the cause of infantile-onset transient hypomyelination. To date, four TMEM63A variants have been reported in five patients. These patients exhibited favorable clinical course, developmental progress, and completion of myelination.Case reportThe patient was a 5-year-old girl with severe global developmental delay, absent speech, no turning over, no gazing, hypotonia, and daily episodes of autonomic seizures. Brain MRI showed hypomyelination of deep and subcortical white matter that appeared hyperintense in T2-weighted imaging from 2 months of age and that showed no change at 4 years of age. Exome sequencing of the patient and her parents revealed a novel de novo missense variant, NM_014698.3:c.1658G>T, p.(Gly553Val), in the TMEM63A gene, which was confirmed by Sanger sequencing. The variant has not been registered in public databases, and it substitutes a highly conserved glycine residue located in a pore-lining transmembrane helix. No other candidate variants were identified.ConclusionsAlthough TMEM63A variants are generally thought to cause transient hypomyelination with favorable developmental progress, identification of a de novo TMEM63A variant in our patient suggests that the TMEM63A-related clinical spectrum is broad and includes severe developmental delay with seizures.     

Magnetic resonance imaging in neonates with total asphyxia

Magnetic resonance (MR) findings in cases of total asphyxia, whose lesions are mainly in the brainstem and deep nuclei, have not been clarified. In this study, we investigated MR images in neonates with total asphyxia. MR images of six infants (three males and three females; gestational age, 35–39 weeks; birth weights, 1880–3572 g) with total asphyxia were examined. In all subjects, neonatal cortical MR lesions were limited to the hippocampus with highlighting on T1-weighted imaging (T1-WI). The neonatal MR lesions of the cerebral white matter were limited to the white matter between the insula and putamen in four infants, and were diffusely involved in two infants. The ventral lateral nucleus of the thalamus was hyperintense on T1-WI in all of the subjects. Other nuclei in the thalamus, the globus pallidus and the putamen were involved in neonatal MR images of all subjects. High intensity areas on T2- weighted imaging were observed at the dorsal areas in the midbrain, pons and medulla oblongata in all or most of the subjects at the neonatal period. Also, high intensity areas on T1-WI were observed in the tegmentum of the pons and the midbrain in five cases. Neonates with total asphyxia had lesions mainly in the tegmentem of the brainstem, thalamus, putamen and globus palludus. Some of the infants had extensive lesions of the white matter.     

Reversible White Matter Lesions During Ketogenic Diet Therapy in Glucose Transporter 1 Deficiency Syndrome

BackgroundGlucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport.PatientsWe describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene.ResultsWe initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet.ConclusionsThis is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome.     

A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3

Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically‐confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high‐resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3‐T scanner. We used Tract‐Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel‐based morphometry of infratentorial structures. T2‐relaxometry of cerebellum was performed with in‐house–developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel‐based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2‐relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients. © 2013 Movement Disorder Society     

Diffusion tensor imaging: tract based spatial statistics study in essential tremor

IntroductionEssential tremor (ET) is a common movement disorder with motor and non-motor symptoms. We aimed to investigate the neurodegenerative changes in the brain white matter of patients with ET using Diffusion Tensor Imaging (DTI).MethodsClinical and MRI data from 20 patients (5 women and 15 men; age-38.2 ± 16.5 yrs) with ET and 17 controls (3 women and 14 men; age-40.7 ± 16.5 yrs) were collected prospectively. The DTI data were analyzed using tract based spatial statistics (TBSS) software for tract wise analysis. Further region of interest (ROI) analysis was carried out in the genu of corpus callosum, anterior limb of internal capsule (ALIC), corticospinal tract (CS), and cerebellar peduncles. Effect of tremor severity, disease duration and age of onset on DTI metrics was also studied.ResultsPatients with ET in comparison to controls showed significant (P_corrected < 0.05) increase of mean diffusivityand radial diffusivity in right frontoparietal white matter. Axial diffusivity increase was seen in bilateral cerebral hemispheres, thalamus, brainstem and cerebellar hemisphere white matter. No significant change in fractional anisotropy of the white matter was seen. ROI analysis also revealed abnormalities in the ALIC and cerebellar peduncles. There was no correlation between the severity of white matter changes and clinical tremor severity score as well as disease duration.ConclusionsThis study provides in vivo evidence for axonal disintegration of the cerebral and cerebellar white matter fibres in patients with ET.     

Hypertensive encephalopathy involving the brainstem and deep structures: a case report

Hypertensive encephalopathy rarely presented with widespread edema in the cerebral white matters, deep structures and whole brainstem. A 80-year-old woman manifested as high arterial blood pressure, visual disturbance, severe headache, nausea, and vomiting. T2-weighted and fluid-attenuated inversion recovery magnetic resonance imaging showed high signal-intensity lesions in the cerebral white matter, cerebellum, basal ganglia, thalamus, and brainstem. Diffusion-weighted brain MRI did not show hyperintense signals in these lesions. These findings suggested the pathological basis of vasogenic edema. After control of hypertension, clinical symptoms and these edematous lesions on MRI gradually reduced.     

Correlation between blink reflex abnormalities and magnetic resonance imaging findings in patients with multiple sclerosis

This study investigates the correlation between brain magnetic resonance imaging findings and blink reflex abnormalities in patients with relapsing remitting multiple sclerosis. Twenty-six patients and 17 healthy subjects were included in this study. Blink reflex test (BRT) results were obtained using right and left stimulations; thus, 52 BRT results were recorded for the patient group, and 34 BRT results were recorded for the control group. The magnetic resonance imaging (MRI) findings were classified based on the existence of brainstem lesions (hyperintense lesion on T2 weighted (W) and fast fluid-attenuated inversion recovery MRI or contrast-enhancing lesion on T1W MRI). Correlation analysis was performed for the BRT and MRI findings. The percentage of individuals with abnormal BRT results (including R1 latency, ipsilateral R2 latency, and contralateral R2 latency) was significantly higher in the patient group as compared to the control group (p values: 0.015, 0.001, and 0.002, respectively). Correlation analysis revealed significant correlations between contralateral R2 latency abnormalities and brainstem lesions (p value: 0.011). Our results showed significant correlation correlations between contralateral R2 latency abnormalities and brainstem lesions and these results may be explained the effects of multiple demyelinating lesions of the brain stem of patients with relapsing remitting multiple sclerosis.     

Development of gray matter atrophy in relapsing–remitting multiple sclerosis is not gender dependent: Results of a 5-year follow-up study

ObjectivesThe aim of this study was to explore the evolution of MRI related gender differences in patients with relapsing–remitting (RR) multiple sclerosis (MS) who participated in a clinical trial over the 5 years.Methods181 patients (39 males and 142 females) were assessed for clinical and neuroradiological disease activity over a period of 5 years. Clinical and MRI examination were performed at the baseline, 6, 12, 24, 36, 48 and 60 months. Longitudinal percentage volume changes in whole brain (PBVC), gray matter (PGMVC) white matter (PWMVC) cortex (PCVC), and lateral ventricles (PLVVC) were calculated by using direct methods (SIENA and SIENAX-multitimepoint). Absolute tissue volume changes of subcortical deep GM structures including caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala and nucleus accumbens were estimated using FIRST, a model based segmentation/registration tool. T2 lesion volume (T2-LV) and lesion activity analyses were performed, using a contouring-threshold and subtraction techniques. All clinical and MRI variables were analyzed between males and females.ResultsGlobal (PBVC) and tissue specific (PGMVC, PWMVC, PCVC, PLVVC) brain volume changes showed no significant gender differences over the 5-year follow-up period. Although total subcortical deep GM, caudate, putamen, globus palidus, thalamus and nucleus accumbens normalized volumes were significantly larger in male subjects at baseline, the follow-up analysis showed no differences over the 5 years. There were no gender differences in lesion activity or T2-LV changes over the 5 years.ConclusionNo MRI lesion, global, tissue specific or regional brain volume gender change differences were found over the 5-year follow-up.     

White Matter Lesions in Children and Adolescents With Migraine

BackgroundThe etiology and clinical importance of white matter lesions in migraine remain poorly understood. To understand these issues more fully, we reviewed the brain magnetic resonance imaging scans of pediatric patients and assessed the relationships between white matter lesions, migraine type, patent foramen ovale, and right-to-left shunting.MethodsThe magnetic resonance imaging scans of a cohort of children (n = 89) and adolescents, ages 6 to 18 years, who participated in a study of migraine and patent foramen ovale were reviewed. All children in the cohort had undergone saline contrast transthoracic echocardiography and transcranial Doppler studies.ResultsWhite matter lesions were detected in 15 of the 89 patients (17%). White matter lesions were small (<5 mm) in the majority (10/15; 66%). We observed no relationship between the presence of white matter lesions and (1) migraine type (six patients with white matter lesions among 35 with migraine with aura [17%] vs. nine with white matter lesions among 54 without aura [17%]; P = 1.0); (2) patent foramen ovale (five with white matter lesions among 35 with patent foramen ovale [14%] vs. 10 with white matter lesions among 54 without patent foramen ovale [19%]; P = 0.77); or (3) shunt size (two large shunts in 15 with white matter lesions [13%] vs. nine large shunts among 72 without white matter lesions [13%]; P = 1.0).ConclusionsThese results indicate that small white matter lesions are not infrequent in children and adolescents with migraine. However, no relationships between white matter lesions and migraine type, patent foramen ovale, or degree of right-to-left shunting were observed.     

Correlation Between White Matter Lesions and Intelligence Quotient in Patients With Congenital Cytomegalovirus Infection

BackgroundIt is well known that congenital cytomegalovirus infection exhibits white matter and other types of lesions in magnetic resonance imaging (MRI), but little is known on the clinical significance of white matter lesions because they are also present in asymptomatic congenital cytomegalovirus infection. We investigated for relationships among white matter lesions, intelligence quotient, and other neurodevelopmental features.MethodsNine children (five boys and four girls; mean age: 87.4 months, range: 63-127 months) with sensorineural hearing loss (five bilateral and four unilateral) had been diagnosed as having congenital cytomegalovirus infection by positive polymerase chain reaction findings of dried umbilical cords. They were evaluated for the presence of autistic features, tested using Wechsler Intelligence Scale for Children–Fourth Edition for intelligence quotient, and underwent brain MRI to measure white matter lesion localization and volume.ResultsAt the time of MRI examination (mean age: 69.4 months, range: 19-92 months), white matter lesions were detected in eight of nine patients. Five subjects were diagnosed as having autism spectrum disorders. We observed increased white matter lesion volume was associated with lower intelligence quotient scores (R² = 0.533, P = 0.026) but not with autism spectrum disorders.ConclusionsIn individuals with congenital cytomegalovirus, an increased white matter lesion volume is associated with lower intelligence quotient scores but not with an increased likelihood of autistic behavior.     

Longitudinal stability of progression-related microglial activity during teriflunomide treatment in patients with multiple sclerosis

Background and purpose

The aim was to study brain innate immune cell activation in teriflunomide-treated patients with relapsing–remitting multiple sclerosis.

Methods

Imaging with 18-kDa translocator protein positron emission tomography (TSPO-PET) using the [¹¹C]PK11195 radioligand was employed to assess microglial activity in the white matter, thalamus and areas surrounding chronic white matter lesions in 12 patients with relapsing–remitting multiple sclerosis who had been treated with teriflunomide for at least 6 months before inclusion. Magnetic resonance imaging (MRI) was used to measure lesion load and brain volume, and quantitative susceptibility mapping (QSM) was used to detect iron rim lesions. These evaluations were repeated after 1 year of inclusion. Twelve age- and gender-matched healthy control subjects were imaged for comparison.

Results

Half of the patients had iron rim lesions. In TSPO-PET, the proportion of active voxels indicating innate immune cell activation was slightly greater amongst patients compared with healthy individuals (7.7% vs. 5.4%, p = 0.033). The mean distribution volume ratio of [¹¹C]PK11195 was not significantly different in the normal-appearing white matter or thalamus amongst patients versus controls. Amongst the treated patients, no significant alteration was observed in positron emission tomography distribution volume ratio, the proportion of active voxels, the number of iron-rim-positive lesions, lesion load or brain volume during follow-up.

Conclusions

Compared to controls, treated patients exhibited modest signs of diffuse innate immune cell activity, which was unaltered during follow-up. Lesion-associated smoldering inflammation was negligible at both timepoints. To our knowledge, this is the first study applying both TSPO-PET and QSM-MRI to longitudinally evaluate smoldering inflammation.     

多发性硬化的MRI特征

目的 探讨多发性硬化(MS)患者脑及脊髓的MRI特征.方法 回顾性分析110例临床确诊的MS患者的MRI检查资料.结果 MS患者脑部病灶以侧脑室旁白质多见(55.8%),其次是额叶深部白质(54.7%)、顶叶深部白质(44.2%)、脑干(25.6%)、基底节(23.3%)、丘脑(11.6%)等,灰质也可受累;病灶大小不一,形态可为斑片状、斑点状、圆形、类圆形.脊髓病灶以颈、胸髓多见,分别占75.0%和68.8%,形态可为斑片状、条片状、类圆形,脊髓灰白质可同时受累,10.0%的患者出现脊髓形态改变,如增粗、萎缩.MS患者脑及脊髓内病灶在影像学上因病程不同可表现为长T1、长T2或等T1、长T2信号.结论 MS的MRI特点主要是以脑和脊髓白质出现多个大小、形状不同的病灶.     

A case of chronic infantile type of fucosidosis: clinical and magnetic resonance image findings

Fucosidosis is a rare autosomal recessive disorder resulting from a deficiency of alpha-L-fucosidase. In this report, we describe clinical and magnetic resonance image (MRI) findings of a chronic infantile type patient heterozygous for a nonsense mutation and a large deletion. The disease onset occurred at 2-3 years of age. She was bound to a wheelchair at 6 years of age, and developed dystonia at the age of 13 years. Brain MRI at 13 years of age showed marked cerebral and cerebellar atrophy, high intensities in the white matter of the frontal and occipital lobes, and low intensities of the bilateral thalamus, striatum, substantia nigra, red nucleus and mamillary bodies on T2-weighted images. The low intensities of basal ganglia on T2-weighted images seems characteristic of lesions in fucosidosis.     

Magnetic Resonance Imaging Findings in Japanese Encephalitis

Ten patients with Japanese encephalitis diagnosed by serological criteria underwent magnetic resonance imaging (MRI) in axial and coronal sections. In 6, a second MRI study was done. The MRI findings were compared with the clinical outcome. Four patients died within several months of onset, 2 had sequelae such as hemiparesis and dementia, and the remaining 4 had no sequelae. In 9 of 10 patients, either diffuse or patchy white matter lesions were observed bilaterally, together with abnormalities in areas such as the thalamus, basal ganglia, and brainstem. For 3 patients who died or remained demented, the second MRI revealed extensive, diffuse white matter abnormalities. This study indicates that Japanese encephalitis can produce white matter involvement, although gray matter structures such as the thalamus, basal ganglia, and brainstem are more severely affected. The severity of these MRI lesions correlated with the clinical outcome.     

Subtle white matter injury is common in term-born infants with a wide range of risks

Objectives

Perinatal hypoxia–ischaemia affects cognitive outcomes of infants even when clinical symptoms were latent and intensive care was not required. We performed a retrospective analysis in a cohort of term infants who required intensive care (i) to investigate the incidence of abnormal white matter appearances on the magnetic resonance imaging obtained before 2 months corrected age, and (ii) to examine its relationships with other cerebral lesions, clinical backgrounds, and short-term outcome at 12 months.

Study design

White matter appearances on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery imaging (FLAIR) were assessed in relationship with other cerebral lesions, clinical backgrounds, established white matter lesions on follow-up scans, and abbreviated developmental outcomes at 12 months in 150 term-born infants who were cared for at a tertiary neonatal intensive care unit with mixed indications for admission (positive pressure ventilation and intravenous inotropes required in 38% and 49% of infants respectively).

Results

On T2WI and FLAIR, 14.0% and 41.3% of infants showed abnormal white matter intensities respectively, which were both related with lesions in the internal capsule and deep grey matter. Abnormal T2WI appearances were correlated with low Apgar scores and low blood base-excess whereas abnormal FLAIR appearances were associated with younger corrected age at scan. Follow-up studies in a cohort of infants revealed that abnormal white matter intensities further correlated with chronic long-T2 lesions after 8 months corrected age (n = 40) and severe neuro-developmental disability at 12 months (n = 104).

Conclusions

Abnormal white matter intensities were associated with pathological clinical variables. White matter injury may not be a specific form of cerebral damage in preterm infants. For the precise evaluation of newborn brain imaging, it may be beneficial to account for corrected age even in term infants.     

Electrophysiological evaluation of tremors secondary to space occupying lesions and trauma: Correlation with nature and sites of lesions

BackgroundElectrophysiological evaluation of tremor secondary to intracranial space occupying lesions (SOL) and cranial trauma may provide information regarding pathophysiology of tremors.ObjectivesTo compare the electrophysiological characteristics of tremor secondary to SOL and trauma and to correlate tremor characteristics with sites of lesion, and types of SOL.MethodsMulti-channel tremor recording and MRI were performed in 18 patients with predominantly tremor secondary to SOL (F: M = 5:6; age ± SD: 26.6 ± 15.0 years) and following trauma (7 men; age: 27.3 ± 11.0 years).ResultsIn both groups, there was a wide range in the frequency of tremor (2.5–7.5 Hz in the SOL group and 2–7.5 Hz in the post-trauma group) and a strong inverse correlation of the frequency with the duration of EMG bursts (SOL group: r = 0.8, p = 0.004; post-trauma group: r = 0.9, p = 0.02). While all the patients with SOL had regular EMG bursts (synchronous – 54.6%, alternating – 27.3%, mixed – 18.2%), 85.7% of post-trauma patients had irregular EMG bursts (synchronous – 42.9%, alternating – 14.3%, mixed – 42.9%). In SOL group, those with predominantly intrinsic destructive lesions of brainstem, thalamus, or basal ganglia (n = 7) had a statistically significant lower mean frequency of tremor than those (n = 4) with either extrinsic or intrinsic compressive lesions (3.5 ± 0.9 Hz vs 6.7 ± 0.6 Hz; p = 0.0001). In the post-trauma group, the patients with additional lesions in thalamus or striatum, apart from white and grey matter lesions had lower mean tremor frequency (3.7 ± 1.0 Hz vs 6.1 ± 1.5 Hz; p = 0.05).ConclusionsThe electrophysiological characteristics of tremor secondary to SOL and trauma differ and correlate with the nature and sites of lesions. This information, which need to be validated in larger cohort of patients, may be useful in understanding the pathogenesis of tremor.     

Correlation between White Matter Hyperintensities Related Gray Matter Volume and Cognition in Cerebral Small Vessel Disease

Background and AimThe relationship between severity of cerebral small vessel disease, as defined by white matter hyperintensities classification, and gray matter volume of different brain regions has not been well defined. This study aimed to investigate brain regions with significant differences in gray matter volume associated with different degrees of white matter hyperintensities in patients with cerebral small vessel disease. Meanwhile, we examined whether correlations existed between gray matter volume in different brain regions and cognitive ability.Methods110 cerebral small vessel disease patients underwent 3.0T Magnetic resonance imaging scans and neuropsychological cognitive assessments. White matter hyperintensities of each subject was graded according to Fazekas grade scale and was divided into two groups: (A) White matter hyperintensities score of 1–2 points (n = 64), (B) White matter hyperintensities score of 3–6 points (n = 46). Gray matter volume was analyzed using voxel-based morphometry implemented in Statistical Parametric Mapping 12 software.ResultsBrain regions with significant differences in gray matter volume between groups were diffused throughout the brain. Patients with high white matter hyperintensities scores exhibited decreased gray matter volume in some subregions of the frontal lobes, the temporal lobes, the parahippocampal gyrus, hippocampus and thalamus (p < 0.05). Among them, gray matter volume in the ventrolateral area of right inferior temporal gyrus, together with the right posterior parietal and occipital thalamus were positively correlated with Montreal Cognitive Assessment scores (p < 0.05). Gray matter volume in the extreme ventrolateral area of right inferior temporal gyrus along with the entorhinal cortex of left parahippocampal gyrus were positively correlated with both Montreal Cognitive Assessment and Mini-Mental Status Examination scores (p < 0.05).ConclusionsCerebral small vessel disease is considered as a whole brain disease and local white matter lesions can influence the gray matter in remote areas. Reducing the severity and progression of white matter hyperintensities may help to prevent secondary brain atrophy and cognitive impairment.     

Congenital muscular dystrophy with dropped head phenotype and cognitive impairment due to a novel mutation in the LMNA gene

Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect almost all organs of the human body including striated muscle. For lamin-related congenital muscular dystrophy two different phenotypes are known to date. Here, we describe a 3-year-old, white Caucasian girl with a novel de novo mutation in the LMNA gene with marked hypotonia of neck and trunk muscles with dropped head posture, loss of cervical lordosis and marked joint laxity. In addition to this novel mutation, the patient also had cerebral white matter lesions on MRI and cognitive impairment on developmental testing. This is only the second A-type lamin-related congenital muscular dystrophy patient in which white matter lesions are described. Thus, white matter involvement might be a feature in A-type lamin-related congenital muscular dystrophy, warranting screening of these patients for both white matter lesions and cognitive impairment.