Hereditary neuropathy with liability to pressure palsy

Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disease with sensory and motor nerve palsies usually precipitated by trivial trauma or compression. In the majority of cases HNPP is caused by deletion of the peripheral myelin protein 22 gene (PMP22) on chromosome 17p11.2. The authors present a family case with genetically proven HNPP.     

Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies

Hereditary neuropathy with liability to pressure palsies (HNPP) provides a human model to investigate the role of PMP22 in myelinated peripheral nerve, since the disease is caused by a deletion of one of the two PMP22 alleles. To systematically characterize the phenotype of HNPP, we prospectively evaluated the clinical features and electrophysiological findings in 17 genetically confirmed patients, 7 men and 10 women, ranging in age from 9 to 66 years (mean, 41 +/- 13). Fifteen symptomatic patients presented with episodes of transient focal weakness or sensory loss that were usually related to particular activities causing nerve compression, including stretching or minor repetitive focal trauma. No patient sought medical attention for symptoms of a symmetric polyneuropathy. Neurological examinations were either normal or mildly abnormal. Neither focal slowing of nerve conduction studies, nor reduction in compound muscle action potential (CMAP) or sensory nerve action potential (SNAP) amplitudes consistently predicted the site of symptoms. We conclude that the majority of patients with HNPP present with transient, recurrent, focal symptoms of weakness or sensory loss in the distribution of individual nerves or plexus, and that a diffuse symmetric sensorimotor polyneuropathy is an unusual presentation of HNPP. These studies suggest that the function of PMP22, at least in part, is to stabilize myelin so that it will be protected from injuries resulting from repetitive, minor trauma.     

Fulminant case of hereditary neuropathy with liability to pressure palsy

Hereditary neuropathy with liability to pressure palsy (HNPP) is typified as isolated nerve palsies caused by trivial compression or trauma. It rarely presents in two extremities and even more infrequently affects all four limbs simultaneously. We present a patient who concurrently experienced right shoulder, left hand, and bilateral foot weakness mimicking several multifocal conditions. Electromyography suggested HNPP and subsequent nerve biopsy and genetic testing were confirmatory. The case demonstrates that HNPP can present in a fulminant manner and should be included in the differential diagnosis of acute multiple mononeuropathies. The possible causes for such a rapid clinical course in our patient are discussed.     

A report of hereditary neuropathy with liability to pressure palsy (HNPP) presenting with brachial plexopathy: the value of complete electrodiagnostic testing

Patients with hereditary neuropathy with liability to pressure palsy (HNPP) typically present with a mononeuropathy (particularly peroneal or ulnar palsy) or a brachial plexopathy. Careful electrodiagnostic testing has an important role in establishing the diagnosis of HNPP differentiating this condition from other inherited or acquired neuropathies as well as obviating the need for unnecessary surgeries. We present a case of a patient who presented with a painless brachial plexopathy who was found to have multiple sites of segmental demyelination on nerve conduction studies, consistent with HNPP. We review the clinical and electrodiagnostic features of HNPP including the key electrodiagnostic findings to screen for this disorder.     

Clinical and electrophysiologic features of HNPP patients with 17p11.2 deletion

OBJECTIVES: Although the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) is important for correct prognostic evaluation and genetic counseling, the diagnosis is frequently missed or delayed. Our main aim on undertaking this study was to characterize the electrodiagnostic features of HNPP. MATERIAL AND METHODS: Clinical, electrophysiologic and molecular studies were performed on Korean HNPP patients with 17p11.2 deletion. The results of electrophysiologic studies were compared with those of Charcot-Marie-Tooth disease type 1 A (CMT1A) patients carrying 17p11.2 duplication. RESULTS: Eight HNPP (50 motor, 39 sensory nerves) and six CMT1A (28 motor, 16 sensory nerves) patients were included. Sensory nerve conduction was slow in 97% of HNPP nerves. Motor nerve conduction at common entrapment sites was also abnormally slow in 87.5%, whereas at non-entrapment sites conduction slowing was infrequent. Distal motor latency (DML) was prolonged in 80% of HNPP nerves, and terminal latency index (TLI) was significantly lower in HNPP than in normal controls and in CMT1A patients (P < 0.01). In contrast to CMT1A, where severity of nerve conduction slowing was not different among nerve groups, HNPP sensory nerve conduction was more slowed in the median and ulnar nerves than in the sural nerve (P < 0.01), and DML was more prolonged in the median nerve than in the other motor nerves (P < 0.01). TLIs were significantly lower in HNPP than in the normal control and CMT1A patients for the median and ulnar nerves (P < 0.01), and were also significantly reduced for the peroneal nerve (P < 0.05) compared with those of the normal controls. CONCLUSION: HNPP is characterized electrophysiologically by a generalized neuropathy, superimposed by focal entrapment neuropathies. The slowing of sensory conduction in nearly all nerves and the distal accentuation of motor conduction abnormalities are the main features of background polyneuropathy in HNPP. The distribution and severity of the background electrophysiologic abnormalities are closely related to the topography of common entrapment or compression sites, which suggests the possible pathogenetic role of subclinical pressure injury at these sites in the development of the distinct background polyneuropathy in HNPP.     

Age associated axonal features in HNPP with 17p11.2 deletion in Japan

OBJECTIVE: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy (HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities. METHODS: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls. RESULTS: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination. CONCLUSIONS: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.     

Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies

OBJECTIVE: Because diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) frequently is missed or delayed, we looked for electrodiagnostic features that raise suspicion of the disorder by making comparisons with two more common diseases that mimic it electrophysiologically: chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetic polyneuropathy. METHODS: A retrospective review of the neuromuscular laboratory database was performed. RESULTS: Nine HNPP subjects, 22 with CIDP and 49 with diabetic polyneuropathy. Of all the HNPP nerves studied, abnormally slow sensory nerve conduction velocity (SNCV) was found in 93%, prolonged distal motor latencies (DML) in 78%, slow motor nerve conduction velocity in 31%, and prolonged F-wave latencies in 90%. Mean SNCV for HNPP was 85.6%+/-10.6% of the lower limit of normal and significantly slower than for CIDP (114.3%+/-20.1%; p<0.0001) or diabetes (108.1%+/-14.8%; p<0.0001). Excluding the carpal tunnel site from the analysis did not alter this observation: Mean DML were more prolonged in HNPP, even without median nerve data in the analysis (118.5%+/-31.0% of the upper limit of normal), than in CIDP (103.2%+/-31.6%; p<0.05) or diabetes (86.3%+/-18.3%; p<0.0001). Mean HNPP motor nerve conduction velocity was within normal limits. CONCLUSIONS: According to findings, hereditary neuropathy with liability to pressure palsies (HNPP) has a distinctive background polyneuropathy independent of superimposed entrapment neuropathy. It is characterized by diffuse sensory nerve conduction velocity (SNCV) slowing and prolongation of distal motor latencies with relatively infrequent and minor reduction of motor nerve conduction velocities. This indicates disproportionate distal conduction slowing in the disorder.     

Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent sensory or motor manifestations. The molecular basis of HNPP is a deletion on chromosome 17p11.2. We studied a family (father, 61 years; mother, 55 years; 6 children of mean age 25.3 years) showing symptoms of carpal tunnel syndrome in 4 members (the parents and 2 sons). No one of them reported episodes of nerve palsy. In all the patients, except the mother and the younger son, electrophysiologic evaluation showed a sensorimotor polyneuropathy with delayed sensorimotor latencies. Genetic analysis was carried out in the parents and the eldest son. The 17p11.2 deletion was detected in the father and son, indicating paternal transmission of the disease. Clinical manifestations of HNPP may be atypical. Sometimes there is no history of acute nerve palsy, as in this family. For this reason, the frequence of HNPP might be underestimated. Electrophysiological examination is of great importance for the diagnosis of HNPP. Genetic analysis is a rapid and reliable diagnostic tool that can be combined with simplified electrophysiological examination, avoiding the need for nerve biopsy. In conclusion, the diagnosis of HNPP should be invoked in early onset entrapment neuropathies. Received: 8 November 2002 / Accepted in revised form: 28 March 2003 Correspondence to: R. Del Colle     

遗传性压迫易感性神经病(4例临床与病理)

目的从临床、电生理及病理方面对遗传性压迫易感性神经病（ＨＮＰＰ）进行探讨,以提高对本病的认识。方法４例经临床及腓肠神经活检确诊,肌电图检测临床受累或未受累的肢体的感觉或运动传导速度;腓肠神经活检标本分别做ＨＥ、Ｍａｓｏｎ染色和Ｆｌｅｍｍｉｎｇ染色光镜观察。结果肌电图为广泛神经传导异常,甚至出现在临床未受累的神经支配区;腓神经活检显示部分神经纤维明显增粗,轴索正常。结论ＨＮＰＰ与遗传关系密切,但也有散发,电生理检查是重要的筛选手段,神经活检见到髓鞘增粗或典型的腊肠样结构是重要的确诊手段     

儿童遗传性压迫易感性周围神经病的临床、肌电图与基因特征(附1例报告)

目的探讨儿童遗传性压迫易感性周围神经病(HNPP)的临床、EMG与基因特点。方法报道基因诊断明确的1例HNNP,并结合文献分析HNPP的临床、EMG与基因特点。结果患儿,女,11岁8个月,于入院10 d前运动后出现左足麻木,不能背屈,查EMG提示多发性周围神经源性损害。患儿父亲及伯父有类似病史。患儿基因检查示chr17:14095421~15458636杂合缺失,大小1363.2kb,诊断HNPP。结论轻微牵拉或压迫后出现肢体无力患儿,及早进行EMG检查,对于周围神经损害广泛而肢体麻痹局限,且有类似家族史的患儿,应注意HNPP,并进行基因检查。     

Entrapment in anti myelin-associated glycoprotein neuropathy

Anti-myelin associated glycoprotein (MAG) neuropathy is a chronic disorder in which IgM antibodies react with Schwann cell glycoproteins, including MAG and peripheral myelin protein 22 (PMP22). Nerve conduction studies show features of axon loss and predominantly distal slowing consistent with demyelination. Because a genetic loss of PMP22 function yields hereditary neuropathy with liability to pressure palsies (HNPP), loss of PMP22 function due to anti- MAG antibodies may result in increased sensitivity to entrapment. We investigated this by performing standardized electrophysiological studies in 16 patients with anti- MAG neuropathy and 16 disease controls with genetically confirmed HNPP. Disproportionate slowing relative to adjacent segments occurred in similar proportions of patients with anti-MAG neuropathy and HNPP, and was of the same magnitude in each group. Affected were the elbow, carpal tunnel and the wrist-hand segments of the median and ulnar nerves. However, in anti- MAG neuropathy as compared to HNPP, absolute values of distal motor latencies and conduction velocities outside entrapment sites were slower and amplitudes were lower. In conclusion, increased sensitivity for entrapment may occur in anti-MAG neuropathy and contribute to part of the nerve damage.     

遗传性压力敏感性周围神经病

遗传性压力敏感性周围神经病（HNPP）是一种常染色体显性遗传的周围神经病。HNPP的分子基础是染色体17p11．2区的一个1．5Mb片段缺失。临床特点为反复发作的在易卡压部位神经受压后，受累神经所支配区域出现运动感觉障碍。本病早期准确诊断后采取预防措施可减少发作。本文就HNPP的病因、临床特点及诊断等作一综述。     

Peroneal neuropathy after weight loss

The objectives of this study were to evaluate the clinical and electrophysiological findings in peroneal mononeuropathies following a weight-reduction diet. Thirty patients with acute peroneal palsy and weight loss were studied. Complete nerve conduction studies (NCS) were performed in upper and lower limbs. NCS showed conduction block (CB) of the peroneal nerve at the fibular head that recovered in 29 patients within 3 weeks to 3 months. Severity of CB was correlated with clinical weakness. Three patients had abnormalities consistent with polyneuropathy (PNP). NCS in asymptomatic relatives confirmed familial neuropathy. Nerve biopsy and molecular study were consistent with hereditary neuropathy with liability to pressure palsies (HNPP). One of these peroneal palsies (6 months) recovered after neurolysis. Weight loss might be a risk factor in peroneal mononeuropathies. NCS is a tool in the diagnosis of the site and severity of the nerve injury. Testing should be considered for relatives of patients with PNP because peroneal mononeuropathies may be the first expression of HNPP.     

Hereditary neuropathy with liability to pressure palsy in patients under 30 years old: Neurophysiological data and proposed electrodiagnostic criteria

Introduction: In young patients with mononeuropathy who lack family history and precipitating factors, hereditary neuropathy with liability to pressure palsy (HNPP) may be a possibility. Our objective is to propose neurophysiological criteria for HNPP in patients <30 years of age. Methods: We conducted a national multicenter retrospective clinical and neurophysiological study in patients under 30 with genetically confirmed HNPP. Results: All of the 51 patients included in the study had at least 1 demyelinating pattern in 2 asymptomatic nerves, and 3 abnormalities were found in almost 90%, including slowed motor nerve conduction velocity across the elbow in at least 1 ulnar nerve (97.5%), increased distal motor latency (DML) in at least 1 fibular nerve (95.8%), and increased DML in both median nerves (89%). Age influenced DML slightly only in the fibular nerve. Discussion: Dissemination of nerve involvement in HNPP incites to perform a complete nerve conduction study. including bilateral ulnar, fibular, and median nerves. Muscle Nerve 57 : 217–221, 2018     

Clinical and electrodiagnostic findings, nerve biopsy and blood group markers in a family with hereditary neuropathy with liability to pressure palsies

Clinical, electrophysiologic and biopsy findings as well as studies of blood group markers in a family with hereditary neuropathy with liability to pressure palsies (HNPP) are reported. There was an autosomal dominant trait without genetic linkage between the HNPP gene and blood group markers controlled by chromosome 1. Reduced motor and sensory nerve conduction velocity was found in clinically affected and unaffected nerves. Characteristic morphological changes in sural nerve biopsy including tomaculous swelling were present.     

Hereditary neuropathy with liability to pressure palsy combined with schwannomas of the median and medial plantar nerves

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 in a Turkish patient (HNPP): a rare cause of entrapment neuropathies in young adults

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant nerve disease usually caused by 1,5 Mb deletion on chromosome 17p11.2.2-p12, the region where the PMP-22 gene is located. The patients with HNPP usually have relapsing and remitting entrapment neuropathies due to compression. We present a 14-year-old male who had acute onset, right-sided ulnar nerve entrapment at the elbow. He had electrophysiological findings of bilateral ulnar nerve entrapments (more severe at the right side) at the elbow and bilateral median nerve entrapment at the wrist. Genetic tests of the patient demonstrated deletions in the 17p11.2 region. The patient underwent decompressive surgery for ulnar nerve entrapment at the elbow and completely recovered two months after the event. Although HNPP is extremely rare, it should be taken into consideration in young adults with entrapment neuropathies.     

Sonographic features in hereditary neuropathy with liability to pressure palsies

Introduction: Diagnostic nerve ultrasound is becoming more commonly used by both radiologists and clinicians. The features of different neuromuscular conditions must be described to broaden our understanding and ability to interpret findings. Methods: Our study examines the sonographic features of 7 subjects with hereditary neuropathy with liability to pressure palsies (HNPP) in comparison to 32 controls by measuring the nerve cross‐sectional area (CSA) of the median, ulnar and tibial nerves. Results: Significant differences (P < 0.05) in nerve size were found. The HNPP group had a larger CSA for the median nerve at the wrist and ulnar nerve at the elbow (entrapment sites), but not the forearms. The tibial nerve at the ankle was also larger in the HNPP group, suggesting possible concomitant tibial neuropathy at the ankle. Conclusion: These results will help shape imaging protocols to better detect conditions with non‐uniform nerve enlargements. Muscle Nerve 2011     

Sonographic and electrodiagnostic features of hereditary neuropathy with liability to pressure palsies

In hereditary neuropathy with liability to pressure palsies (HNPP), the increase in distal motor latencies (DMLs) is often out of proportion to the slowing of conduction velocities, but the pathophysiological mechanism is still unclear. We used a combined electrophysiological and ultrasonographic (US) approach to provide insight into this issue. Twelve HNPP subjects underwent extensive electrophysiological studies and US measurements of the cross‐sectional area (CSA) of several peripheral nerves. US nerve enlargement was only observed in the carpal tunnel, Guyon's canal, the elbow and the fibular head. We did not observe US abnormalities at sites where nerve entrapment is uncommon. An increase in DMLs was observed regardless of US nerve enlargement. The increased nerve CSA only in common sites of entrapment likely reflected the well‐documented nerve vulnerability to mechanical stress in HNPP. No morphometric changes were seen in the distal nerve segments where compression/entrapment is unlikely, despite the fact that the DMLs were increased. These data suggest that factors other than mechanical stress are responsible for the distal slowing of action potential propagation. We speculate that a mixture of mechanical insults and an axon‐initiated process in the distal nerves underlies the distal slowing and/or conduction failure in HNPP.     

Carpal tunnel syndrome in childhood: study of 6 cases

Six children, 4 girls and two boys, aged 5–14 years, with carpal tunnel syndrome (CTS) are reported. Median nerve entrapment had different aetiologies in each case. One patient developed unilateral CTS symptoms after intensive basketball training. He improved upon terminating this sporting activity. In 3 patients bilateral CTS was associated with Schwartz-Jampel syndrome, trigger finger and mucopolysaccharidosis I (MPS IS=Scheie syndrome), respectively. The latter subject, a boy aged 11 years who had severe bilateral muscle thenar weakness and atrophy, made a good recovery after surgery. Two cases with bilateral CTS had autosomal dominant disease. One of them showed familial CTS with thickening of the transverse carpal ligament. The other child (5 years old) presented early bilateral CTS as first manifestation of hereditary neuropathy with liability to pressure palsies (HNPP). His relatives were asymptomatic, but they showed electrophysiological and nerve biopsy changes consistent with HNPP. Nerve conduction studies (NCS) are diagnostic in paediatric CTS. Moreover, NCS is an objective method to evaluate the evolution of the nerve lesions after surgery. NCS must be performed in nerves of the propositus other than the median, as well as in first degree symptomatic and asymptomatic relatives in order to identify possible familial neuropathies.