RESUMEN
Carpal and cubital tunnel syndromes are the two most common compressive neuropathies, but both carpal and cubital tunnel syndromes are extremely rare in children. Therefore, the combination of carpal and cubital tunnel syndrome in the pediatric population is even more uncommon. These neuropathies have multiple causes, with the three main categories being mechanical injury, metabolic, and idiopathic. Here, we present the unique case of a 15-year-old female with no known genetic or physical risk factors who was diagnosed with atraumatic combined carpal and cubital tunnel syndrome with severe, chronic nerve entrapment and damage. After nearly two years of conservative management, the patient had a cubital tunnel and carpal tunnel release simultaneously. The transverse carpal ligament was grossly thickened intraoperatively, leading to difficulty in the identification of the median nerve. The ulnar nerve was severely compressed and flattened. Following decompression, both nerves continued to be erythematous and inflamed. After surgery, the patient had barriers to getting appropriate postoperative care. Specifically, the patient was unable to attend physical and hand therapy appointments, possibly leading to continued weakness, numbness, and intermittent pain. In our patient, the preoperative workup did not illuminate the severity of the median and ulnar nerve damage, possibly delaying surgical intervention. In addition to our case, we utilized the TriNetX database (TriNetX, Inc., Cambridge, Massachusetts, United States) to investigate the rate and treatment of compressive neuropathies in the pediatric population. The database was queried for pediatric patients who underwent carpal tunnel release, cubital tunnel release, and pediatric patients with both carpal and cubital tunnel syndrome diagnoses in childhood. We found that there were 20,819,207 pediatric patients on the TriNetX database, of whom 503 (0.002%) were diagnosed with both carpal and cubital tunnel syndrome. Based on our case and the current literature, a thorough history of pediatric patients with suspected carpal or cubital tunnel syndrome should include an evaluation of family history and activity level for pertinent risk factors. Widening the scope of the patient history could allow for more timely surgical intervention and improve long-term outcomes for the pediatric population. When evaluating children for either carpal tunnel or cubital tunnel syndrome, we recommend that healthcare providers evaluate both neuropathies simultaneously.
RESUMEN
Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with genetically African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago Territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European genetic ancestry, the highest Native American genetic ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was -8 melanin units. Derived allele frequencies of SLC24A5A111T and SLC45A2L374F were 0.14 and 0.06, with single allele effect sizes of -6 and -4, respectively. Native American genetic ancestry by itself reduced pigmentation by more than 20 melanin units (range 24-29). The responsible hypopigmenting genetic variants remain to be identified, since none of the published polymorphisms predicted in prior literature to affect skin color in Native Americans caused detectable hypopigmentation in the Kalinago.
The variation in skin colour of modern humans is a product of thousands of years of natural selection. All human ancestry can be traced back to African populations, which were dark-skinned to protect them from the intense UV rays of the sun. Over time, humans spread to other parts of the world, and people in the northern latitudes with lower UV developed lighter skin through natural selection. This was likely driven by a need for vitamin D, which requires UV rays for production. Separate genetic mechanisms were involved in the evolution of lighter skin in each of the two main branches of human migration: the European branch (which includes peoples on the Indian subcontinent and Europe) and the East Asian branch (which includes East Asia and the Americas). A variant of the gene SLC24A5 is the primary contributor to lighter skin colour in the European branch, but a corresponding variant driving light skin colour evolution in the East Asian branch remains to be identified. One obstacle to finding such variants is the high prevalence of European ancestry in most people groups, which makes it difficult to separate the influence of European genes from those of other populations. To overcome this issue, Ang et al. studied a population that had a high proportion of Native American and African ancestors, but a relatively small proportion of European ancestors, the Kalinago people. The Kalinago live on the island of Dominica, one of the last Caribbean islands to be colonised by Europeans. Ang et al. were able to collect hundreds of skin pigmentation measurements and DNA samples of the Kalinago, to trace the effect of Native American ancestry on skin colour. Genetic analysis confirmed their oral history records of primarily Native American (55%) one of the highest of any Caribbean population studied to date compared with African (32%) and European (12%) ancestries. Native American ancestry had the highest effect on pigmentation and reduced it by more than 20 melanin units, while the European mutations in the genes SLC24A5 and SLC45A2 and an African gene variant for albinism only contributed 5, 4 and 8 melanin units, respectively. However, none of the so far published gene candidates responsible for skin lightening in Native Americans caused a detectable effect. Therefore, the gene responsible for lighter skin in Native Americans/East Asians has yet to be identified. The work of Ang et al. represents an important step in deciphering the genetic basis of lighter skin colour in Native Americans or East Asians. A better understanding of the genetics of skin pigmentation may help to identify why, for example, East Asians are less susceptible to melanoma than Europeans, despite both having a lighter skin colour. It may also further acceptance of how variations in human skin tones are the result of human migration, random genetic variation, and natural selection for pigmentation in different solar environments.