Inherited nail diseases

<p class="article-intro">Nail signs due to inherited conditions can be present at birth or develop later in life. It is very important not to miss them, especially when they present as an isolated finding. Sometimes, they can provide the earliest sign by which a condition may be identified. Moreover, understanding the embryological defect is mandatory to avoid including any secondary nail change in the primary disorder and to anticipate possible complications. </p> <p class="article-content"><div id="keypoints"> <h2>Keypoints</h2> <ul> <li>Nail signs due to inherited conditions may be present at birth or may develop later in life.</li> <li>Do not limit a consultation to the nails &ndash; they are often a clue or the first sign for a hidden condition.</li> <li>Not every inherited nail disorder belongs to a syndrome.</li> <li>Understanding the embryological defect is mandatory to avoid including any seconda ry nail change in the primary disorder and to anticipate possible complications.</li> <li>If medical or surgical treatment is not an option, it is mandatory to provide an appropriate nail care to pa&shy; tients and their caregivers.</li> </ul> </div> <p>Childhood nail diseases are a rather uncommon cause of dermatological consultation: they may be inherited, congenital or acquired. The aim of this paper is however a focus on inherited nail disease only.^1,2 It is very important to keep in mind that inherited diseases differ from congenital diseases.<br /> Congenital anomalies are the result of one or more genetic, infectious, nutritional, environmental or unknown factors. Some congenital abnormalities can also be prevented. Inherited nail diseases can be transmitted following an autosomal dominant (AD), an autosomal recessive (AR), or an X-linked pattern, dominant or recessive (XD and XR).<br /> Before evaluating any nail disorder, it is always of uttermost importance to know the anatomy and physiology of the nail apparatus in order to differentiate pathology from physiology.³ However, this goes beyond the scope of this paper that is, as stated before, to describe the most common inherited nail disorders and others that should be taken into consideration.</p> <h2>Inherited nail diseases affecting only the nails</h2> <p><strong>Nonsyndromic congenital nail disorders</strong><br /> Coilonychia (spoon nails), clubbing, trachyonychia (twenty&shy;nail dystrophy), onycholysis, leukonychia, anonychia, micronychia, brachyonychia and polydactily (from double lunula to double finger/toe) are all nail dystrophies that can be transmitted in an AD or an AR pattern; so, more than one family members is affected by the same abnormality. Although fingernails/toenails bone abnormalities might be associated⁴, the nail dystrophy generally is the major feature.<br /> It is important to remember that anonychia and micronychia at birth can also be the result of drugs (anticonvulsants, anticoagulants, morphine) taken by the mother during pregnancy. For this reason, when this abnormality occurs, it is advisable to check the mother&rsquo;s history before drawing conclusions.</p> <p><strong>Onychodysplasia of the index finger (Iso-Kikuchi disease)</strong><br /> This nail deformity belongs to this group because it affects one or both index fingers and occasionally other fingers, like the 3^rd finger, but no other organ, including the skin. The affected nails usually show micronychia or hemi-onychogryphosis, but anonychia may also be present. The defect is characteristically more pronounced on the radial (medial) side of the nail.^5,6<br /> Possible causes for this disorder are an in-utero ischemia of the radial digital artery, thinner and more delicate than the ulnar one, or an abnormal finger grip (thumb-on-finger instead of finger-on-thumb). The AD pattern of inheritance has also been reported, besides the congenital form, but the genetic loci are still under investigation.⁷ Diagnosis is clinical but an X&shy;-ray may serve as a confirmation showing a Y-&shy;shaped bifurcation of the distal phalanx on lateral projection.</p> <p><strong>Malalignment of the big toenail</strong><br /> This is another condition where only the nails are involved. In particular, the nail plate of the big toe deviates laterally from the longitudinal axis of the distal phalanx,⁸ probably due to an improper in-&shy;utero positioning or an increased tension of the extensor tendon of the hallux. An AD pattern of inheritance has been supposed but never demonstrated. This condition is always reported to be rare, but it is probably under-reported due to misdiagnosis.⁹ Repetitive daily traumatic injuries to the toenails during gait, improper shoes and the malalignment itself compromise the clinical aspect of the nail plate that becomes thick, yellow&ndash;brown in color and presents transverse ridging (Beau&rsquo;s lines) due to intermittent nail matrix damage (Fig.1). Different degrees of severity are possible, depending on the severity of the malalignment and the time of diagnosis. An early diagnosis permits to reduce traumatisms on the nail plate and complications like paronychia, distal nail embedding, ingrowing toenails and permanent onycholysis.<br /> The condition can be monolateral or bilateral. Corrective surgery is a dilemma: whether it should be done early (&lt;2 yrs) and only in milder cases to ensure a good outcome or one should wait and see if the problem will self-correct, is still debated. A total self-correction is rare but im provement with age, especially if the diagnosis is done early and corrective measures are taken, is possible. Surgery means undermining the entire nail bed and matrix and rotating it on the dorsal aspect of the phalanx in order to return the alignment of the long axis of the nail with that of the distal phalanx.^10,11 This diagnosis should always be considered in children with dystrophic or ingrowing toenails. Isolated thickening of the big toenail can also mask a late-onset epidermolysis bullosa, but blisters usually occur at first around the nails, so it is always advisable to take a look at this area before performing a definitive diagnosis.</p> <p><img src="/custom/img/files/files_datafiles_data_Zeitungen_2019_Leading Opinions_Derma_1903_Weblinks_lo_derma_1903_s41_fig1_iorizzo.jpg" alt="" width="375" height="314" /></p> <h2>Inherited nail diseases affecting the nails and other organs</h2> <p><strong>Epidermolysis bullosa </strong><br /> In epidermolysis bullosa, nail changes are common, even though they are not specific to any of the epidermolysis bullosa subtypes (simplex, dystrophic, junctional).¹² Nail blistering, erosions, pachyonychia, onychogryphosis, nail atrophy and anonychia are all possible dystrophies. All of them are exacerbated by trauma.<br /> The AD forms start at birth, the AR ones appear between the ages of 6 and 8 years. There is no cure for nail dystrophies due to epidermolysis bullosae, but guidelines of care have been recently published¹³ for patients and caregivers.<br /> Other clinical features of epidermolysis bullosa include blisters on the hands, feet, elbows, knees and mouth, the loss of finger patterns, hypodontia and dental caries. The diagnosis is not always easy,¹⁴ but the greatest challenge is when the diagnosis is occult and the only clue is a family history of acquired childhood nail dystrophy of the big toes (Fig. 2).</p> <p><img src="/custom/img/files/files_datafiles_data_Zeitungen_2019_Leading Opinions_Derma_1903_Weblinks_lo_derma_1903_s42_fig2_iorizzo.jpg" alt="" width="500" height="391" /></p> <p><strong>Nail-patella syndrome </strong><br /> In this condition, which is due to a mutation of the LIM homeobox transcription factor 1-beta (LMX1B) gene and which is inherited in an AD pattern, nail abnormalities are associated with bone and kidney impairments. Glaucoma and deafness are also a possible association. Nail abnormalities may be limited to the thumbs or affect all fingernails. The affected digits may show absence/hypoplasia of the nail plate or mild nail plate dystrophy, usually more marked on the ulnar (lateral) portion of the nail plate. Triangular lunulae are also characteristic. Mild nail changes may cause minor discomfort and go unrecognized. Thus, the diagnosis is delayed putting patients at risk of developing a severe nephropathy (renal involvement is reported in 30&ndash;50 % of patients with 10 % developing end stage renal failure).¹⁵ Bone abnormalities characteristic of this syndrome include absent or hypoplastic patella, radial head abnormalities and iliac horns.¹⁶</p> <p><strong>Ectodermal dysplasias</strong><br /> Ectodermal dysplasias are abnormalities in two or more of the ectodermal derived structures (nails, hair, teeth, sweat glands). Other organs including the skin may be involved. Several disorders are included in this group and more than 150 genes are involved. Nail abnormalities in ectodermal dysplasias may vary from simple brittleness to severe dystrophy.</p> <p><em>Pachyonychia congenita</em><br /> Pachyonychia congenita is an ectodermal dysplasia inherited in an AD pattern and appears due to a mutation in the keratin (KRT) gene 6a, 6b, 6c, 16 or 17. KRT6a and KRT17 mutations affect nails more severely than others with nail thickening, nail bed hyperkeratosis, onycholysis and slow nail growth (Fig. 3). In some mutations, like in the KRT6c gene, nails are not affected at all.<br /> Associated clinical features include palmo-plantar painful hyperkeratosis, follicular hyperkeratosis, oral leukokeratosis, hoarseness and natal teeth preservation.¹⁷ Changes are present at birth in 50 % of cases, but the disease fully manifests only after 5 years of age. Then, plantar keratoderma is seen in around 70 % of children. This has been characterized as a neuropathic pain and due to its extreme discomfort, it has become the treatment target. At the plantar level the hyperkeratosis can be so painful that the gait is impaired. In some cases, pachyonychia congenita may affect only a few digits or present with subtle nail changes (mild distal onycholysis and splinter haemorrhages) that could go easily unrecognized (Fig. 4).¹⁸ <br /> The ectodermal dysplasia most commonly confused with pachyonychia congenita is hidrotic ectodermal dysplasia (Clouston syndrome), but presence of hearing loss and thin, sparse hair during childhood are not typical of pachyonychia congenita.</p> <p><img src="/custom/img/files/files_datafiles_data_Zeitungen_2019_Leading Opinions_Derma_1903_Weblinks_lo_derma_1903_s43_fig3_iorizzo.jpg" alt="" width="375" height="313" /></p> <p><img src="/custom/img/files/files_datafiles_data_Zeitungen_2019_Leading Opinions_Derma_1903_Weblinks_lo_derma_1903_s43_fig4_iorizzo.jpg" alt="" width="500" height="365" /></p> <h2>Inherited diseases where the nails might be affected</h2> <p>Darier-White disease, neurofibromatosis type 1, pytiriasis rubra pilaris, tuberous sclerosis and Lesch&ndash;Nyhan syndrome are disorders where nails might be involved and nail examination may help in the diagnosis. Please note, however, that nail unit alterations in Lesch&ndash;Nyhan syndrome are due to self-mutilation and not genetically induced.</p></p> <p class="article-footer"> <a class="literatur" data-toggle="collapse" href="#collapseLiteratur" aria-expanded="false" aria-controls="collapseLiteratur" >Literatur</a> <div class="collapse" id="collapseLiteratur"> <p><strong>1</strong> Telfer NR et al.: Congenital and hereditary nail dystrophies: an embryological approach to classification. Clin Exp Dermatol 1988; 13: 160-63 <strong>2</strong> Khan S et al.: Genetics of human isolated hereditary nail disorders. Br J Dermatol 2015; 173: 922-9 <strong>3</strong> Sibinga MS: Observations on growth of fingernails in health and disease. Pediatrics 1959; 24: 225-33 <strong>4</strong> Baran R, Juhlin L: Bone dependent nail formation. Br j Dermatol 1986; 114: 371-7 <strong>5</strong> Iso R: Congenital nail defects of the index finger and reconstructive surgery. Seikei Geka 1969; 20: 1383-4 <strong>6</strong> Kikuchi I et al.: Congenital onychodysplasia of the index fingers. Arch Dermatol 1974; 110: 743-69 <strong>7</strong> Hamm HS et al.: Isolated congenital nail dysplasia: a new autosomal dominant condition. Arch Dermatol 2000; 136:1239-43 <strong>8</strong> Baran R, Bureau H: Congenital malalignment of the big toenail as a cause of ingrowing toenail in infancy. Pathology and treatment (a study of 30 cases). Clin Exp Dermatol 1983; 8: 619-23<strong> 9</strong> Catalfo P et al.: Congenital malalignment of the great toenails: a review. Skin Appendage Disord 2018; 4: 230-5 <strong>10</strong> Baran R, Haneke E: Etiology and treatment of nail malalignment. Dermatol Surg 1998; 24: 719-21 <strong>11</strong> Richert B et al.: Cosmetic surgery for congenital nail deformities. J Cosm Dermatol 2008; 7: 304-8 <strong>12</strong> Fine JD et al.: Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014; 70: 1103-26 <strong>13</strong> Kahn MT et al.: Foot care in epydermolysis bullosa: evidence-based guidelines. Br J Dermatol 2019; Epub ahead of print <strong>14</strong> Has C et al.: Clinical guidelines for laboratory diagnosis of epidermolysis bullosa. Br J Dermatol 2019; Epub ahead of print <strong>15</strong> Starace M et al.: A double case of nail patella syndrome in the same family: the importance of nail changes as diagnostic clues for renal involvement. Skin Appendag Disord 2019; 5: 405-8 <strong>16</strong> Itin PH et al.: Missing creases of distal finger joints as a diagnostic clue of nail-patella syndrome. Dermatology 2006; 213: 153-5 <strong>17</strong> Shah S et al.: Pachyonychia congenita in pediatric patients: natural history, features, and impact. JAMA Dermatol 2014; 150: 146-53 <strong>18</strong> Iorizzo M et al.: Pachyonychia congenita Type 1 presenting with subtle nail changes. Pediatr Dermatol 2009; 26: 492-3</p> </div> </p>