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Chronic inflammatory demyelinating polyneuropathy (CIDP) is a symmetric distal muscle weakness and sensory deficit accompanied with diminished or absent deep tendon reflexes. Hereditary neuropathy with liability to pressure palsies (HNPP) is a hereditary neuropathy presenting with transient muscle weakness and sensory symptoms after exposure to pressure or prolonged use in the affected area.

The clinical onset of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rarely reported. On the basis of a 5-year-old affected patient, we reviewed the cases reported in the literature to evaluate the clinical and genetic characteristics of patients with an early onset (

Resume Introduction La neuropathie hereditaire avec hypersensibilite a la pression (NHHP) est une neuropathie peripherique autosomique dominante caracterisee par des neuropathies compressives focales et une polyneuropathie demyelinisante sensitivo-motrice sous-jacente. Elle est habituellement liee a une deletion de 1.5 Mb sur le chromosome 17p11.2 incluant le gene PMP22. Observation Nous rapportons le cas d’une patiente de 31 ans sans antecedents familiaux qui presenta un tableau de polyneuropathie demyelinisante aigue des quatre membres avec hyperproteinorachie apparu dans les suites d’une affection virale, compatible avec une polyradiculonevrite aigue inflammatoire (PRNAI, syndrome de Guillain-Barre). L’examen electrophysiologique mettait cependant en evidence des signes d’atteinte nerveuse aux points de compression (canal carpien et coude) qui nous firent evoquer une NHHP, confirmee ulterieurement par les etudes genetiques. Conclusion Ce cas demontre que la NHHP peut se presenter sous la forme d’une PRNAI.

Resume Propos. – La valeur diagnostique du profil neurophysiologique classique est etudiee dans les differents phenotypes de la neuropathie hereditaire sensible a la pression (HNPP). Methodes. – Les donnees cliniques et electrophysiologiques de huit cas dˈHNPP diagnostiques grâce a la presence dˈune deletion en 17p11.2 (sept cas) ou des criteres histologiques classiques (un cas) ont ete analysees. Resultats. – Soixante-trois pour cent des patients ont des antecedents familiaux et 75 % sont de sexe masculin. Lˈâge moyen au moment du diagnostic et du debut presume est respectivement de 27 et 22 ans. Un premier groupe de cinq patients presente la forme clinique habituelle caracterisee par un ou plusieurs episodes de mononeuropathies aigues regressives, avec une localisation inhabituelle dans un cas (atteinte du nerf saphene interne). Au second groupe appartiennent une patiente diabetique presentant une polyneuropathie sensitivomotrice severe, un sujet aux antecedents de quatre paralysies faciales et enfin une patiente asymptomatique. Si le profil neurophysiologique classique est respecte dans les formes habituelles (allongement diffus de latence distale motrice contrastant avec des vitesses de conduction normales ou peu diminuees, ralentissement electif de la conduction dans les zones dˈetroitesse anatomique, reduction de lˈamplitude ou de la conduction distale des potentiels dˈaction sensitifs), les anomalies sont tres discretes dans le cas asymptomatique ou confinees au territoire facial dans celui exprime exclusivement a ce niveau. Enfin le profil neurophysiologique classique nˈest plus individualisable en raison de la severite des anomalies chez la patiente ayant une polyneuropathie. Conclusion. – Ces donnees confirment lˈheterogeneite du phenotype clinique des cas dˈHNPP porteurs de la deletion en 17p11.2 et montrent les limites du profil neurophysiologique classique dans les cas asymptomatiques ou atypiques.

We describe two cases in which multiple sclerosis (MS) occurred in association with tomaculous neuropathy, presenting as chronic, distal sensorimotor polyneuropathy. In Case 1, monoclonal gammopathy of undetermined significance with monoclonal IgG λ reactive against GM1 ganglioside, was also detected. The diagnosis of tomaculous neuropathy was established after sural nerve biopsy. Teased fibers examination revealed focal `sausage-like' thickenings of the myelin sheaths in intact fibers and in fibers with segmental demyelination. Electron microscopy showed them to be due, mostly, to multiple windings of redundant myelin and concentric apposition of numerous lamellae, in contact with an intact myelin sheath. These are the first reported cases of tomaculous neuropathy in patients with MS. Whether the combination of the two conditions is purely coincidental or suggests the possible causal relation between MS and tomaculous neuropathy, is not certain.

The peripheral myelin protein 22 gene (PMP22) encodes an intrinsic membrane protein of compact myelin. Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies. Charcot-Marie-Tooth disease type 1A is a hypertrophic de-remyelinating neuropathy manifesting with peroneal muscular atrophy and uniform, marked, slowing of nerve conduction velocities. Hereditary neuropathy with liability to pressure palsies is a recurrent focal neuropathy with sausage-like myelin thickening (tomacula) and non-uniform nerve conduction velocity changes. Missense or nonsense mutations also cause more severe Charcot-Marie-Tooth disease type 1A forms of infancy or hereditary neuropathy with liability to pressure palsies, but they are presumably very rare. We performed a mutational scanning of PMP22 in 229 index patients (46 familial, 183 isolated) referred for suspected inherited neuropathy. The series included 125 cases with hereditary neuropathy with liability to pressure palsies (mean age 42.5 years), 47 cases with Charcot-Marie-Tooth disease type 1A (motor nerve conduction velocities at median nerve below 38 m/s) (mean age 40.7 years) and 57 cases with Charcot-Marie-Tooth with unknown nerve conduction velocities (mean age 43 years). Preliminary molecular studies ruled out PMP22 duplication or deletion or mutations in a comprehensive panel of Charcot-Marie-Tooth genes. Mutational scanning of PMP22 was done by denaturing high performance liquid chromatography and automated nucleotide sequencing. To investigate the molecular basis of phenotype-to-genotype correlations, we performed a transcriptional analysis of PMP22 using reverse-transcriptase polymerase chain reaction and quantitative real-time polymerase chain reaction in two phenotypically divergent nerve biopsies. Ten patients harboured eight micromutations of PMP22 including four novel changes. In six familial and three sporadic cases, detected mutations caused premature or delayed stop codons and were associated with hereditary neuropathy with liability to pressure palsies; the related pathological pictures ranged from classical tomaculous neuropathy to a mild demyelinating neuropathy with atypical non-tomaculous myelin thickenings. In a single family a c.179-2A> G mutation affecting the splice acceptor site of intron 2 cosegregated with a Charcot-Marie-Tooth disease type 1A-like syndrome and a peculiar pathological picture of demyelinating neuropathy without Charcot-Marie-Tooth disease type 1A-like classical onion bulbs or tomacula. Transcriptional analysis of a novel c.174_178 + 7delAAACGGTGAGGC deletion involving exon 2 and intron 2 demonstrated an unstable mutant transcript leading to a p.Asn59GlyfsX12 change; the mutation represented a null allele and caused a typical tomaculous hereditary neuropathy with liability to pressure palsies. The Charcot-Marie-Tooth disease type 1-like c.179-2A > G allele led to a stable transcript with an in-frame deletion of exon 3 (p.Glu60_Ala106del); the predicted shorter protein could exert variable molecular effects. In conclusion, micromutations of PMP22 cause a clinical and pathological continuum of demyelinating neuropathies that may include atypical phenotypes.

A 42-year-old woman was surgically treated for carpal tunnel syndrome, revealing schwannoma of the median nerve. A year later, she developed a tarsal tunnel syndrome. At time of this diagnosis, hereditary neuropathy with liability to pressure palsies (HNPP) was diagnosed genetically and a schwannoma of the medial plantar nerve was treated surgically. The occurrence of HNPP and schwannomas in the same patient might be purely coincidental, but it is tempting to speculate that they share a common genetic basis.

Hereditary neuropathy with liability to pressure palsies (HNPP) classically occurs as recurrent focal neuropathy. We report the first known instance of HNPP manifesting, over a 15-year period, as a recurrent sensorimotor polyneuropathy and confirmed by the presence of the PMP-22 gene deletion. We suggest that the molecular study of the 17p11.2 region could be an effective non invasive investigative tool in cases of chronic recurrent polyneuropathy associated with episodes of nerve palsy.

The finding of tomacula, focal areas of sausage-shaped hypermyelination in peripheral nerves, is reported for the first time in avian riboflavin deficiency. Day-old, meat-type chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and were killed on postnatal days 6, 11, 16, and 21, while control chickens were fed a conventional diet containing 5.0 mg/kg riboflavin. Tomacula were found in sciatic and brachial nerves from day 11 onward, became more frequent and prominent with increasing time, and preceded the onset of segmental demyelination.

Four children, index cases of families in which autosomal dominant neuropathy with liability to pressure palsies (HNPP) was diagnosed, are presented. Only one child was admitted for evaluation of an acute peroneal palsy, three presented with other symptoms. Polyneuropathy was diagnosed in all four children, in one of their parents and in some sibs. On inquiry, one child and several members of the four families had experienced transient palsies before. Morphological studies of the sural nerves showed frequently large tomacula and a neuropathic process of segmental de- and remyelination, and axonal degeneration. Attention is drawn to the atypical presentation without pressure palsies of HNPP.

Clinical findings suggested an inherited tendency to pressure palsies, but in this case without a family history. This was confirmed pathologically by the identification of a tomaculous neuropathy showing some atypical features including the presence of uncompacted lamellae in a high proportion of fibres.

The appearance of Guillain-Barré syndrome in a 9-year-old girl led to the detection of a hereditary neuropathy in her family. This neuropathy showed clinical and electrophysiological characteristics of Charcot-Marie-Tooth disease. Only nerve biopsy performed in a sister of the proband allowed diagnosis of tomaculous neuropathy which presented unusual clinical, electrophysiological and bioptic aspects.

We describe two patients with associations of hereditary neuropathies and heritable skeletal disorders not previously reported. The first patient had Marfan’s syndrome and hereditary motor and sensory neuropathy Type 1. The second patient had Ehlers-Danlos syndrome, Klippel-Feil syndrome and tomaculous neuropathy.

Background: Carpal tunnel syndrome is a debilitating neuropathy affecting millions of individuals. Although there are published reports of familial associations of carpal tunnel syndrome, the molecular mechanisms are unknown. Objective: To determine the prevalence and potential role of the chromosome 17 microdeletion associated with hereditary neuropathy with liability to pressure palsies in patients diagnosed as having carpal tunnel syndrome. Design: Prospective study. Patients and Methods: Since hereditary neuropathy with liability to pressure palsies may present as carpal tunnel syndrome, we evaluated 50 patients with idiopathic carpal tunnel syndrome for hereditary neuropathy with liability to pressure palsies. Results: No hereditary neuropathy with liability to pressure palsies deletions were detected. Conclusion: Molecular genetic testing for hereditary neuropathy with liability to pressure palsies in patients with idiopathic carpal tunnel syndrome is of limited value.

Introduction Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder of peripheral myelin characterized by episodes of recurrent mononeuropathies usually involving nerves at common sites of entrapment and compression. Additional features include evidence of a diffuse demyelinating sensorimotor polyneuropathy on nerve conduction studies, focal myelin thickening (tomacula) on sural nerve biopsy, and a 1.5 Mb deletion on 17p11.2 encompassing the peripheral myelin protein 22 (PMP22) gene in most families. Patients and methods Two girls, aged 10 and 12 years, presented with peroneal nerve palsy and peroneal nerve palsy plus tibial nerve palsy, respectively. In none case, a clear causal factor was recognizable. Neurophysiological studies: both cases showed diffuse sensory and motor nerve conduction velocity slowing and prolongation of distal motor latencies. In addition, features of focal entrapment neuropathy were obtained at proximal peroneal nerve level. Sural nerve biopsy: large axons demyelination, redundant myelin and intraaxonal looping (case 1) and tomaculas (case 2). Molecular genetics: 17p12-p11 deletion was demonstrated in both affected girls, the mother and two maternal uncles of case 1 and in the father, paternal grandfather and two paternal uncles of case 2. Conclusions NHPP should be suspected in cases of peripheral neuropathy without clearly recognizable cause. Electrophysiological and molecular studies permit both delineation of the condition and identification of otherwise clinically normal family members.

We report a patient with type III Ehlers-Danlos syndrome, presenting with recurrent footdrop, who had electrophysiologic evidence of a conduction block of the common peroneal nerve followed by complete resolution. We feel that this case supports the possible link between Ehlers-Danlos syndrome and multiple pressure sensitive neuropathy (tomaculous neuropathy), alluded to by Schady and Ochoa (1984).

We report on nine cases of tomaculous neuropathy (hereditary neuropathy with liability to pressure palsies). The age at diagnosis is variable (13 to 73). The mostly involved nerves are ESP and radial; recuperation is usual. In a case, this neuropathy is discovered in a patient with periateritis nodosa.

Tomaculous neuropathy (TN) is classically associated with the inherited, recurrent focal neuropathies. We report a case of TN manifesting as an acute recurrent polyneuropathy. A 28-year-old woman had 2 episodes of acute, ascending, symmetrical sensorimotor deficit. Teased nerve-fiber preparation confirmed the presence of TN. Extensive investigations failed to reveal other cause for her symptoms. We believe that this case is unique and broadens the clinical spectrum of TN.

Clinical and neurophysiological studies were carried out in hereditary pressure-sensitive neuropathy. In 4 generations, 19 out of 87 family members were affected. The transmission of the disorder is autosomal dominant with total penetrance but variable expression. The motor conduction velocities of peripheral nerves were slowed even in clinically unaffected nerves. Light- and electron-microscopic studies were performed in the fibular nerve of one patient. A characteristic tomaculous neuropathy was discovered.