Study Reveals Commonality of Rare Neuropathy in Korean Population

Results from a study published in the Orphanet Journal of Rare Diseases this week suggest that the hereditary neuropathy with liability to pressure palsies (HNPP), which has been assumed to be rare, might not be uncommon in the Korean population.

Historical studies in adults have been conducted in the Republic of Ireland, Northern England, Newcastle upon Tyne, and South West Finland and the calculated global prevalence of HNPP was approximately 0.84, 2.0, 7.3, and 16 people per every 100,000, respectively. That was, however, always assumed to be underestimated because of the mild symptoms associated with the autosomal dominant disorder.

Because the signs of HPNN are so mild, adult-onset patients wouldn’t know to visit the hospital for testing. The most common effects of the condition don’t present until the second or third decade of life, and include acute onset of non-painful focal sensory and motor neuropathy in the territory of a single nerve or brachial plexus.

In a study conducted between December 2015 and May 2017, 11,885 newborns were evaluated for constitutional chromosomal abnormalities using the next-generation sequencing (NGS)-based copy number variation (CNV) analysis. Capillary or cord blood was collected and DNA was extracted using standard protocols. In all, more than 6-million sequence reads were analyzed using a bioinformatics platform.

Results of this study concluded that prevalence of the disease was much higher (58.9 per 100,000) than the previously reported numbers. This is likely because the tests were conducted on newborns before the onset of symptoms, while the previous tests were conducted on symptomatic adults.

HNPP is typically the result of a deletion of chromosome 17p11.2 including PMP22 (PMP22 Del HNPP). It is estimated that 80%-90% of individuals with HNPP have the chromosome deletion, and that the remaining individuals have a pathogenic variant of PMP22.

Of the babies tested, 17p11.2 deletions were detected in 7 samples, 65.7% (n=6) of which were female and 42.9% (n=3) of which had a family history of HNPP. All samples were from unrelated families and were collected within a week of birth.

There were, additionally, 2 samples that exhibited PMP22 duplication, a reciprocal phenomenon of PMP22 deletion that can lead to Charcot-Marie-Tooth disease type 1A (CMT1A).

While the study had limitations and the number of subjects may not be adequate enough to estimate the exact prevalence of the rare genetic disorder, it still provides insight regarding the baseline frequency of the chromosome deletion that commonly causes HNPP.

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Reference:

1. Park JE, Noh SJ, Oh M, et al. Frequency of hereditary neuropathy with liability to pressure palsies (HNPP) due to 17p12 deletion in a Korean newborn population. Orphanet Journal of Rare Diseases, 2018; DOI: 10.1186/s13023-018-0779-5.