Abnormal myelination in a patient with deletion 14q11.2q13.1

A male carrying an interstitial deletion of chromosome 14, presumably del(14)(q11.2q13), and presenting with abnormal myelination on magnetic resonance imaging is described. The abnormal myelination was evidenced as a high-signal intensity on T(2)-weighted magnetic resonance imaging. The patient had severe neurologic signs, various dysmorphic features, and a marked microcephaly. To our knowledge, this case is the first patient reported with abnormal myelination and a deletion of chromosome 14.     

A multiple sclerosis-like illness in a man harboring the mtDNA 14484 mutation.

In most cases of Leber's hereditary optic neuropathy (LHON) the only clinical manifestation is visual loss. A multiple sclerosis-like illness has been infrequently reported in association with LHON. Most patients are women harboring the mtDNA 11778 mutation. We present a young man with clinical and paraclinical evidence of a demyelinating process with profound bilateral visual loss who harbored the mtDNA 14484 mutation associated with LHON.     

Unusual clinical presentation of a patient carrying a novel single 1.8 kb deletion of mitochondrial DNA

Kearns-Sayre syndrome (KSS) is a mitochondrial encephalomyopathy characterized by progressive external ophthalmoplegia (PEO), pigmentary retinopathy and onset before the age of 20 years. Cerebellar ataxia, as well as short stature and increased protein content in the cerebrospinal fluid, are frequent additional symptoms. A single large mitochondrial (mt) DNA deletion of 4,977 bp is the most common molecular defect in KSS. Recently, different mutations have also been associated with incomplete, KSS-like phenotypes. We describe the unusual clinical presentation of a patient carrying a novel 1,814-bp deletion of mtDNA. In contrast with typical KSS, the clinical picture of this patient did not include either palpebral ptosis or PEO and was dominated by an ataxic syndrome.     

Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication

We present the case of a patient who developed delusions and auditory hallucinations and was clinically diagnosed as having schizophrenia. Ten years after the onset of schizophrenia, the disease progressed to mild parkinsonism. SNCA duplication was confirmed. This case expands the spectrum of clinical features in carriers of SNCA duplication.     

Abnormal platelet functions in a patient with abetalipoproteinemia

Studies with isolated lipoproteins and washed platelets suggest that lipoproteins may affect platelet functions. We investigated platelet-rich plasma (PRP) from a patient with abetalipoproteinemia (ABL), whose plasma lacks apo-B containing lipoproteins (VLDL, LDL and chylomicrons). ABL-PRP aggregated poorly with different agonists and failed to respond to arachidonate. Thromboxane B2 (TxB2) formation was severely impaired. After gel-filtration most of the aggregation defects persisted in agreement with reduced metabolism of endogenous arachidonate. However, arachidonate-induced aggregation and TxB2 production partially normalized. Normal platelets suspended in ABL-plasma showed similar defects in aggregation and TxB2 production but arachidonate-induced aggregation was much lower than expected on the basis of TxB2. We conclude that the abnormal platelet functions in ABL-PRP are caused by (i) an intrinsic platelet abnormality due to reduced arachidonate mobilization and (ii) a property in ABL plasma that inhibits aggregation partially by trapping the arachidonate and partially by an unidentified mechanism. The latter properties may be the result of the abnormal lipid composition of ABL-plasma.     

Reversion of mtDNA depletion in a patient with TK2 deficiency

Mutations in the thymidine kinase 2 (TK2) gene cause a myopathic form of the mitochondrial DNA depletion syndrome (MDS). Here, the authors report the unusual clinical, biochemical, and molecular findings in a 14-year-old patient in whom pathogenic mutations were identified in the TK2 gene. This report extends the phenotypic expression of primary TK2 deficiency and suggests that factors other than TK2 may modify expression of the clinical phenotype in patients with MDS syndrome.     

Single-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis

One possible cause for the neuronal loss in sporadic amyotrophic lateral sclerosis (S-ALS) is an increase of free radicals, which may produce oxidative damage to susceptible biomolecules, which, in turn, can damage the mitochondrial DNA (mtDNA). Following laser microdissection of single motor neurons from paraffin-embedded autopsy tissue, we analyzed the presence of a common mtDNA deletion, the 5 kb common deletion (CD). Spinal cord neurons showed slightly higher CD detection rate in patients than controls (94% vs 75%). No significant differences were found between patients and controls for neurons derived from other motor or non-motor regions. A PCR assay of serial DNA dilutions (10-fold) showed no CD level differences between motor neurons in S-ALS and controls. These data suggest that neuronal death in S-ALS is not associated with significant accumulation of mtDNA deletions.     

Dystonia in a patient with deletion of 18p

18p- syndrome from chromosomal deletion of the short arm of chromosome 18 shows a wide range of clinical manifestations. Mental retardation is the most frequent neurological complication; other neurological deficits are more rarely reported. Only one 18p- patient with focal dystonia at the lower limbs has been reported, while there have beenno reported cases of generalized dystonia. We report a 27-year-old male with 18p-de novo complete deletion (karyotype 46,XY,18p-) who was affected by severe generalized dystonia, hypokinesia, mental retardation and dysmorphic features. The 18p- syndrome should be added to the list of genetic causes of secondary dystonia. A karyotype analysis should be considered in secondary dystonias, particularly when there are associated dysmorphic features and mental retardation.     

Abnormal musical pacemaker in a patient with musical hallucinations

Music creation requires a highly orchestrated temporal pattern. The study of a patient with repetitive musical hallucinations enabled us to examine temporal pacemakers in music production. Here, we show that the pattern of faster silent production of a chosen tune compared with its production aloud was reversed when the patient produced the hallucinatory tune. This observation might suggest the utilization of a pacemaker(s), which functions differentially during the disease.     

Unusual clinical presentations in patients harboring the facioscapulohumeral dystrophy 4q35 deletion

Facioscapulohumeral dystrophy (FSHD) is a dominantly inherited myopathy usually associated with a deletion at locus 4q35. Typically, FSHD patients present with a recognizable constellation of signs including weakness of facial, shoulder and pelvic girdle, humeral, and anterior foreleg muscles; preservation of some muscles including the deltoids; and other characteristic features including prominent scapular winging, anterior axillary folds, and horizontally positioned clavicles. We performed clinical and FSHD genetic studies on four patients with atypical clinical features who were cared for at a regional neuromuscular center. The four patients, each harboring 4q35 deletions, presented with atypical phenotypes including facial-sparing scapular myopathy, limb-girdle muscular dystrophy, distal myopathy, and asymmetric brachial weakness. This report demonstrates the expanding clinical heterogeneity in patients harboring the 4q35 deletion.     

Hematological abnormalities in a patient with a 22q11.2 deletion

We report a case of a 28-year-old man carrying a 22q11.2 deletion and presenting with giant platelets, thrombocytopenia and leukocyte inclusion bodies. In our patient, platelet glycoproteins were normally expressed on membranes and platelet function was preserved. The May-Hegglin anomaly or Sebastian syndrome associated with the 22q11.2 deletion was suggested. Atypical features also included the lack of any cardiovascular defect, T cell deficit or palate anomaly, generally common with this deletion.     

Abnormal responses to succinylcholine and pancuronium in a patient with hemiparesis

Supersensitivity to depolarization produced by succinylcholine and resistance to pancuronium were observed in paretic muscles of a patient with a right frontoparietal tumor. The abnormal sensitivity to relaxants is compared with observations reported in patients with myasthenia gravis and hemiparesis. We hypothesize that upper motoneuron dysfunction may be followed by the appearance of “new” junctional receptors, which may occasion a supersensitivity to depolarization and a poor affinity for both curare and anti-acetylcholine-receptor antibodies. A decrease in acetylcholinesterase activity of “decentralized” muscles should also be considered.

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Sommario Ipersensibilità all'effetto depolarizzante della succinilcolina e resistenza all'effetto paralizzante del pancuronio vengono osservate nella muscolatura paretica di un paziente di 72 anni nel corso di un intervento neurochirurgico per la rimozione di un tumore fronto-parietale destro. La duplice anomalia della risposta viene paragonata alle osservazioni effettuate in pazienti nei quali coesistono miastenia gravis ed emiparesi da lesione centrale. Viene formulata l'ipotesi che la disfunzione del motoneurone centrale possa essere seguita dalla comparsa di “nuovi” recettori acetilcolinici giunzionali dotati di ipersensibilità alla depolarizzazione e di scarsa affinità per il curaro e per gli anticorpi antirecettore. Come ipotesi alternativa viene considerata la possibilità che le risposte anomale esibite dalla muscolatura “decentralizzata” siano attribuibili ad una riduzione dell'acetilcolinesterasi provocata dalla lesione neurologica.