Familial true leukonychia: A case report with review of the literature

INTRODUCTION

True leukonychia is a rare nail disorder characterised by persistent white discoloration of the nail plate resulting from abnormalities in the nail matrix.^[1,2] It can present in various forms, including total, partial, transverse, longitudinal or punctate, and is classified as true, apparent or pseudoleukonychia based on the site of pathology.^[1,2] In true leukonychia, the whitening remains unchanged with pressure and does not migrate distally with nail growth, distinguishing it from other types.^[3,4] Although punctate leukonychia is relatively common in children, idiopathic total forms are uncommon and familial cases are exceedingly rare.^[5] Recognition of familial patterns is important, as the condition is benign, non-progressive, and requires no treatment, but can be mistaken for systemic disease or fungal infection, leading to unnecessary investigations. This report describes two brothers with long-standing, non-syndromic familial true leukonychia of all fingernails, highlighting the clinical features, diagnosis and the importance of awareness of this rare presentation.

We also conducted a literature search to identify published reports of hereditary, familial, or idiopathic true leukonychia. The databases PubMed, Scopus and Google Scholar were searched from inception to March 2025. The keywords and Medical Subject Headings used in combination included ‘Leukonychia’, ‘Nails’, ‘Hereditary Diseases’, ‘Familial’, ‘Idiopathic’, and ‘True leukonychia’. Search queries were combined using Boolean operators e.g., (Leukonychia OR ‘true leukonychia’) AND (hereditary OR familial OR idiopathic) AND (nails).

The search included case reports or case series describing true leukonychia; or reports of hereditary, familial or idiopathic aetiology published in English language. Reports describing acquired leukonychia secondary to trauma, systemic disease or medication; or non-English articles; or those without an available full text were excluded.

Reference lists of retrieved articles were manually screened to identify additional relevant publications. A total of 23 relevant reports were included, spanning from historical cases to recent publications.

CASE REPORT

A 25-year-old male presented with a history of white fingernails since early childhood, first noticed by his family. According to his parents, the change was first noted when he was approximately 3 years old and had been non-progressive thereafter. There was no history of illness, fever, drug intake, trauma or chemical exposure preceding the onset. The patient denied any associated pain, tenderness, brittleness or shedding of nails. He had never sought treatment and the nail appearance had remained unchanged throughout life.

He reported no other symptoms suggestive of systemic disease, including no gastrointestinal disturbances, skin rash, oral mucosal lesions, hair loss, abnormal sweating or dental abnormalities. His past medical history was unremarkable. He had never used chronic medication and denied tobacco, alcohol or illicit drug use. There was no history of malnutrition or restrictive diets.

Family history revealed that his older brother, now aged 29 years, developed the same nail changes at a similar age, with identical persistence and absence of symptoms. Both siblings were born to healthy, non-consanguineous parents. No other relatives in two generations had nail changes, and there was no known family history of dermatologic disorders, genetic syndromes or metabolic disease. A family pedigree chart was not constructed, as there were no other affected relatives beyond the two siblings, and such an illustration was deemed non-essential.

On general examination, both brothers appeared healthy. Systemic, dermatologic and developmental assessments were within normal limits. Nail examination revealed total leukonychia of all fingernails in both brothers [Figure 1]. The nails were smooth, porcelain white, and non-blanching, with intact cuticles, normal periungual tissue and absence of pitting, thickening, ridging or detachment; dermoscopic features are shown in Figure 2. The lunulae were not visible. There was no subungual debris. All toenails were normal. No changes were noted in hair, teeth or skin.

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Figure 1:

Familial true leukonychia in two brothers. (a) Clinical photograph of a 25-year-old male patient (older brother) presenting with porcelain-white fingernails affecting all digits, sparing the toenails. (b) Clinical photograph of a 29-year-old male patient (younger brother) presenting with porcelain-white fingernails affecting all digits, sparing the toenails.

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Figure 2:

Dermoscopic features of familial true leukonychia in two brothers showing homogenous, porcelain-white fingernails affecting all digits, accentuated lunula, smooth nail surface and clear distal nail borders, consistent with true leukonychia. [DermLite DL1, polarized mode, 10× magnification]

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To exclude secondary causes, we performed a comprehensive laboratory workup, including complete blood count, serum zinc, calcium, magnesium, Vitamin B12 and thyroid function tests, along with liver and renal profiles; all results were normal. Direct microscopy and fungal cultures from nail clippings were negative.

With normal laboratory values, absence of systemic or syndromic features and a positive family history, a diagnosis of familial true leukonychia totalis was made. Genetic testing was not performed and is acknowledged as a limitation. Given the benign and non-progressive nature of the condition, no treatment was prescribed. The brothers were reassured and advised to return if any nail changes or new symptoms developed.

DISCUSSION

True leukonychia arises from alterations in the nail matrix that disrupt normal keratinisation. Historically, this phenomenon has been attributed to light-scattering air spaces within the nail plate,^[3] resulting in a uniform, opaque, white appearance that does not fade with pressure, thereby distinguishing it from apparent leukonychia.^[1] However, histopathologic examination – including reports dating back to Unna (1893)^[6] – demonstrated that these air spaces were absent. Instead, nail plate cells contained eosinophilic cytoplasm, differing from the empty-appearing cells of normal nail plates [Figure 3], as also described by Haneke in Histopathology of the Nail – Onychopathology (2017).^[3]

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Figure 3:

Histopathology from Professor Haneke’s archive showing nail plate cells with eosinophilic cytoplasm, characteristic of true leukonychia (haematoxylin–eosin stain, ×200). Arrows indicate areas with eosinophilic cytoplasm.

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While most cases of true leukonychia are acquired secondary to trauma, systemic illness, medications or nutritional deficiencies, some are hereditary. Hereditary leukonychia may present alone or in association with syndromes affecting ectodermal structures such as hair, teeth and skin.^[7] Isolated familial true leukonychia, as in our patients, is exceptionally rare. Genetic studies have identified PLCD1 mutations in several hereditary cases, supporting an autosomal dominant inheritance in these reports, although autosomal recessive patterns have also been described.^[8] Our patients did not undergo genetic testing, which is acknowledged as a limitation.

When compared with other reports, the presentation in these two brothers aligns with cases described by Arsiwala^[9] and Mathachan et al.,^[10] where affected individuals showed complete fingernail involvement, normal toenails and no systemic abnormalities. Inheritance patterns in the literature vary, with most familial cases showing high penetrance. Table 1^[11-29] summarises previously published cases, now expanded to include inheritance patterns, associated features and available treatment outcomes, thereby enhancing comparative value. In our patients, the absence of progression over decades parallels other reports describing lifelong stability without complications.

Treatment responses in true leukonychia have been inconsistent. Occasional improvement has been reported with zinc supplementation or amino acid therapy,^[11] and one case noted spontaneous improvement during pregnancy,^[12] possibly implicating hormonal modulation. However, in patients with normal micronutrient levels and no systemic disease, as in our cases, supplementation has not been shown to alter the course, reinforcing that the condition is benign and requires no intervention.

The key clinical priority is differentiating true leukonychia from apparent leukonychia and pseudoleukonychia to avoid unnecessary investigations or antifungal treatments. Recognising familial patterns not only aids diagnosis but also allows for appropriate reassurance to patients and families. Awareness of this entity among primary care physicians and dermatologists can prevent misdiagnosis and reduce patient anxiety.

The term “idiopathic leukonychia” could also be used because genetic testing was not performed, leaving the exact aetiology undetermined. Although PLCD1 mutations have been linked to hereditary leukonychia, testing could not be conducted in our patients due to economic constraints. Future studies with molecular analysis may clarify the genetic basis in similar familial cases.

CONCLUSION

Familial true leukonychia is a very rare but harmless nail condition, presenting as lifelong, stable white discoloration of the fingernails without systemic associations. Awareness of this benign entity is essential to avoid unnecessary investigations, misdiagnosis as systemic disease or fungal infection and inappropriate treatments. The present report of two affected brothers with identical findings and no other family history highlights the importance of careful history-taking, clinical examination and recognition of familial patterns. While genetic testing was not performed in our patients – representing a limitation – it may help confirm suspected hereditary cases in future studies. In most cases, including ours, no treatment is required; reassurance and periodic observation are sufficient.