Version May 2024
INTRODUCTION — Congenital and hereditary nail diseases are a heterogeneous group of rare disorders that, in most cases, present at birth, although some heritable changes present later in childhood [1,2]. They can occur in isolation (nonsyndromic congenital nail disorders) or as a component of several genetic syndromes (eg, nail-patella syndrome, pachyonychia congenita, ectodermal dysplasia). Congenital nail disorders should not be confused with the physiologic, transitory nail changes that are present at birth in most newborns and typically resolve in the first few months or, rarely, years of life.
This topic will discuss the clinical features, diagnosis, and treatment of the most common congenital and hereditary nail disorders in children. Acquired nail disorders in children are discussed separately. An overview of nail disorders in adults, nail surgery, and nail biopsy are also discussed separately.
●(See "Nail disorders in infants and children: Acquired nail diseases".)
●(See "Overview of nail disorders".)
●(See "Nail biopsy: Indications and techniques".)
●(See "Principles and overview of nail surgery".)
EPIDEMIOLOGY — Congenital and hereditary nail disorders are rare. Their exact prevalence in pediatric populations is unknown. It is estimated that nail abnormalities, including congenital and acquired disorders, account for 3 to 11 percent of pediatric dermatology consultations [3,4].
ANATOMY OF THE NAIL UNIT IN NEWBORNS AND INFANTS — The nail unit is composed of the nail matrix, the nail bed, the proximal and lateral nail folds, and the hyponychium (figure 1). The nail matrix is the germinative epithelium from which nail matrix keratinocytes differentiate to ultimately form the nail plate. Most of the nail matrix is hidden beneath the proximal nail fold, but the distal third is sometimes visible through the proximal portion of the nail plate as a half moon-shaped structure called the lunula. (See "Overview of nail disorders", section on 'Anatomy and physiology of the nail unit'.)
Nail development starts around the 12th to 13th week of gestation and is completed by the 25th week [5]. In newborns, the nails are small, thin, and soft but completely formed. The growth of the nail plate is continuous throughout life, with the speed of growth increasing from birth, reaching the highest value at the age of 10 to 14 years, and then becoming similar to that of young adults (approximately 0.1 to 0.15 mm/day) [6].
In healthy newborns, the fingernails are oval or rectangular in shape, with a longitudinal major axis, and are flat in most cases. The index fingernail measures approximately 5 mm in length and 3.5 mm in width, and the thumbnail is approximately 9 to 10 mm in width. The great toenail often has a trapezoid shape, with a longitudinal major axis, and a distal width larger than the proximal width. In infants and older children, the nail size is related to the age and weight of the child.
The ratio of the width of the nail in the middle of its length to the width of the finger is approximately 0.7 [7]. Micronychia (nail smaller than normal) is defined as a nail-to-finger width ratio <0.5, while macronychia (nail larger than normal) is defined by a ratio >0.8.
PHYSIOLOGIC (TRANSITORY) NAIL CHANGES IN NEWBORNS AND INFANTS
Koilonychia (spoon nails) — The term koilonychia ("spoon nails") describes nails with a transverse and/or longitudinal, central depression and everted lateral edges [8]. Koilonychia of the toenails is frequently idiopathic in newborns (picture 1), especially on the big toe, due to the thin and soft nail plate. It spontaneously regresses in late childhood when the nail plate thickens [6].
Transient, light brown or ocher pigmentation of the proximal nail fold — A transient, light brown or ocher pigmentation of the proximal nail fold extending to the interphalangeal joint can often be seen in newborns with highly pigmented skin. It represents a physiologic, melanic pigmentation that appears in the first six months of life. On dermoscopic examination, it is characterized by a regular, reticular pattern located only in the periungual skin, without involvement of the cuticle or the nail unit [9].
Beau lines of the fingernails — Up to 90 percent of newborns may show a single transverse groove (Beau line) of the fingernails in the first few weeks of life (picture 2) [1]. Beau lines result from an intrauterine distress or physiologic alteration during birth, which interferes with the rate of nail growth, and disappear with growth in the following few months of life.
Transient, physiologic onychoschizia — Transient, physiologic onychoschizia (transverse, lamellar splitting of the free edge of the nail plate) is a common nail plate alteration noted in early infancy on the big toes and thumbs [1].
Congenital hypertrophy of the lateral nail fold of the hallux — Congenital hypertrophy of the lateral nail fold of the hallux is observed in most newborns and is typically associated with an incompletely developed, triangular-shaped toenail (picture 3) [10]. This alteration, which is thought to result from asynchronous growth of the nail plate and surrounding soft tissues, is usually asymptomatic and spontaneously improves over time. However, inflammation from ingrown toenails has been described in a few cases [11,12].
Ingrown nails — Ingrown nails are rare in newborns. However, multiple ingrown fingernails may develop in the first few days of life due to the physiologic grasp reflex [6]. It resolves spontaneously in approximately four months, as the grasp reflex disappears.
Distal embedding of the toenail can also occur due to a thin and short nail plate (picture 4). It usually regresses spontaneously in the first few months of life.
Chevron or herringbone nails — Chevron or herringbone nails are most frequently seen in children at the age of five to seven years but can occur in infants [13]. The nail plate surface shows oblique and longitudinal, diagonal ridges converging distally towards the center of the nail plate, describing a central spine with an appearance of a "V" or a chevron (picture 5). They disappear in early adulthood [14].
NONSYNDROMIC CONGENITAL NAIL DISORDERS — Many types of isolated congenital nail disorders have been described [15]. Data on the genetic alterations underlying these disorders and the patterns of inheritance are limited.
Anonychia/hyponychia — Congenital isolated anonychia (MIM #206800) is a rare, autosomal recessive disorder with variable expression caused by variants in RSPO4, encoding the R-spondin 4, a protein involved in the Wnt/beta-catenin signaling pathway [16-18]. The nail phenotypes range from complete absence of a nail bed to a nail bed of reduced size with absent or rudimentary nail [19,20].
Unilateral or bilateral micronychia of the index finger is a presenting feature of Iso-Kikuchi syndrome (picture 6), a rare, nonhereditary disorder also known as congenital onychodysplasia of the index finger (COIF) [21]. The most common associated bony abnormality is bifurcation of the underlying phalanx, but other unusual cases have been reported [22].
Cases of iatrogenic congenital anonychia with or without digital hypoplasia due to prenatal phenytoin exposure have been reported (picture 7) [23].
Nonsyndromic congenital nail disorder 1 — Nonsyndromic congenital nail disorder 1 (twenty-nail dystrophy; MIM #161050) includes isolated congenital trachyonychia and autosomal recessive nail dysplasia. Both disorders present at birth [24]:
●Congenital trachyonychia – Congenital trachyonychia is characterized by diffuse roughness of the nail plate, with a sandpapered, lusterless appearance or, less frequently, by opalescence and pitting of the nail plate [25]. Familial cases suggest an autosomal dominant pattern of inheritance [26].
●Autosomal recessive nail dysplasia – Autosomal recessive nail dysplasia presents at birth with thickened, hyperplastic, and hyperpigmented nails with a very slow growth rate. In late childhood, the nails appear as claw-like structures. Autosomal recessive nail dysplasia is caused by biallelic mutations in FDZ6, encoding frizzled class receptor 6 [27]
Hereditary leukonychia — Hereditary leukonychia (porcelain nails; MIM #151600) is a rare nail disorder caused by variants in PLCD1 and inherited in an autosomal dominant manner [28-31]. The nails may show white spots (leukonychia punctata) or transverse bands (leukonychia striata) [32].
Congenital malalignment of the great toenail — Congenital malalignment of the great toenail is an uncommon and, probably, under-recognized condition characterized by lateral deviation of the nail plates, which are not parallel to the longitudinal axis of the phalanx, due to lateral rotation of the nail matrix [33]. The condition is usually present at birth (picture 8) but may go unnoticed until nail dystrophy becomes apparent during early childhood [34].
In older children, the great toenails are thick, with a grossly, triangular shape, multiple transverse grooves and ridges, and yellow-brown discoloration, and are partially detached from the nailbed. Spontaneous correction is reported to occur in approximately one-half of the cases [33]. Early surgical correction (before the age of two) with rotation and realignment of the nail apparatus gives the best cosmetic results [35,36].
Congenital curved nail of the fourth toe — Congenital curved nail of the fourth toe (CNFT) is a rare anomaly predominantly reported in countries in Asia and characterized by unilateral or bilateral curvature of the nail plate toward the plantar aspect of the distal phalanx [37,38]. The nail appears thickened, with hyperkeratosis of the hyponychium and nail bed. CNFT is typically associated with hypoplasia or absence of the underlying distal phalanx [39].
Vertical implantation of the nail of the fifth toe — Vertical implantation of the nail of the fifth toe is a rare disorder due to an anomalous implantation of the matrix of the fifth toe, resulting in the vertical growth of the nail [1].
Isolated congenital nail clubbing — Isolated congenital nail clubbing (MIM #119900) is a rare disorder characterized by enlargement of the nail plate and distal segments of the fingers and toes due to abnormal proliferation of the connective tissue of the nail bed. Autosomal recessive variants in two genes have been associated with congenital nail clubbing: HPGD, encoding the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase [40], and SLCO2A1, encoding a major prostaglandin PGE2 transporter [41,42]. Of note, variants in both HPGD and SLCO2A1 have been associated with primary hypertrophic osteoarthropathy [43-45].
Racket thumbs (racket nails) — The term "racket thumb" (or "racquet thumb") refers to an autosomal dominant, congenital malformation of one or both thumbs associated with brachyonychia (nail and nail bed wider than the length of the phalanx) and absence of the lateral nail folds. Racket thumbs may occur as an isolated disorder or in association with numerous genetic disorders, including Rubinstein-Taybi syndrome, Larsen syndrome, and Brooke-Spiegler syndrome. (See "Microdeletion syndromes (chromosomes 12 to 22)", section on '16p13.3 deletion syndrome (Rubinstein-Taybi syndrome)' and "Skeletal dysplasias: Specific disorders", section on 'Larsen syndrome' and "Brooke-Spiegler syndrome (CYLD cutaneous syndrome)".)
SYNDROMIC CONGENITAL NAIL DISORDERS — Congenital nail disorders can occur as a part of complex syndromes involving anomalies in the skin and other epidermal appendages or can be associated with skeletal deformities. Nail abnormalities present with two predominant patterns: nail hypoplasia (anonychia/micronychia) and nail hypertrophy/hyperkeratosis.
Syndromes with associated anonychia/micronychia — Anonychia (absence of nails) and micronychia (nails that are smaller than normal) are features of several genetic multiple malformation syndromes, ectodermal dysplasia, and epidermolysis bullosa (EB) [46-51].
Cooks syndrome — Cooks syndrome is a rare disorder characterized by fingernail hypoplasia or complete absence of fingernails, total absence of toenails, hypoplasia of distal phalanges in hands, and absence of all distal phalanges of feet [46,52].
DOORS syndrome — DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures) syndrome (MIM #220500) is a rare, autosomal recessive disorder of unknown etiology. Most patients present with small or absent nails and hypoplastic terminal phalanges; a triphalangeal thumb is present in one-third of affected patients [47,53].
Coffin-Siris syndrome — Coffin-Siris syndrome is a genetically heterogeneous, multiple malformation syndrome characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and other digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hypertrichosis, and sparse scalp hair [48,49]. Coffin-Siris syndrome has been associated with variants in at least 12 genes encoding subunits of the SWI/SNF complex, a chromatin remodeling factor [54].
Focal dermal hypoplasia (Goltz syndrome) — Focal dermal hypoplasia (MIM #305600) is an X-linked dominant ectodermal dysplasia characterized by patchy skin aplasia, nodular fat herniation, limb anomalies, and multiple cutaneous and extracutaneous abnormalities [50,51]. Longitudinal ridging, micronychia, and/or anonychia are reported in virtually all patients with Goltz syndrome [55]. (See "Focal dermal hypoplasia (Goltz syndrome)".)
Nail-patella syndrome — Nail-patella syndrome (MIM #161200), or hereditary osteo-onychodysplasia, is a rare, autosomal dominant disorder with variable expressivity caused by variants in the LMX1B gene on chromosome 9q34, encoding a transcription factor of the LIM-homeodomain type [56]. Nail-patella syndrome is characterized by the classic clinical tetrad of hypoplastic or absent patella, dysplasia of elbows, iliac horns, and nail and distal digital abnormalities (picture 9) [57,58].
Nail abnormalities are evident at birth in nearly 100 percent of patients with nail-patella syndrome and consist of anonychia or micronychia (absent or thin, fragile nail plates) and triangular lunulae, which are pathognomonic findings. Nail changes are evident in the fingernails and are commonly bilateral and symmetric, with severity decreasing from the first towards the little finger. Severity of signs are variable, and there are inter- and intrafamilial, phenotypic variabilities.
Onychoscopy enhances the visualization of the characteristic, triangular shape of the lunula. The color of the triangular lunula is white, while its dimensions are different in different digits (ie, being more pronounced in the thumbs and less evident going toward the fifth digit (picture 10)) [59].
The clinical presentation, diagnosis, and management of nail-patella syndrome are discussed in detail separately. (See "Nail-patella syndrome".)
Ectodermal dysplasias — Ectodermal dysplasias are a large and heterogeneous group of congenital disorders characterized by abnormal development in two or more structures derived from the embryonic ectoderm, namely the hair, nails, teeth, and sweat glands (table 1).
Nail alterations are not specific and include:
●Nail hypoplasia with subungual hyperkeratosis (most common)
●Anonychia (absence of nails)
●Micronychia
●Nail thinning
●Onycholysis
The pathogenesis, clinical manifestations, diagnosis, and management of ectodermal dysplasias are discussed separately. (See "Ectodermal dysplasias".)
Syndromes associated with nail dystrophy or hyperkeratosis
Epidermolysis bullosa — Epidermolysis bullosa (EB) is a highly heterogeneous group of skin fragility disorders caused by variants in genes encoding proteins critical to the integrity of the structure and function of the dermal-epidermal junction [60]. (See "Epidermolysis bullosa: Epidemiology, pathogenesis, classification, and clinical features" and "Diagnosis of epidermolysis bullosa".)
Nail abnormalities are seen in all types of EB, with the most severe occurring in junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB), and can be used as a distinguishing feature when other causes of skin blistering are being considered [61]. Changes range from relatively mild blistering of the periungual tissues and nail bed of fingernails and toenails to more generalized blistering, nail erosions (picture 11), onychodystrophy with onychogryphosis (thickened, yellowish, longitudinally grooved, markedly curved nail plates), nail thickening and parrot beak nail deformity, or absence of nails (anonychia) due to atrophy and scarring of the nail bed and matrix [62,63].
Blisters of periungual tissues and nail bed are rarely present or minimal at birth but become apparent by the age of 18 months. Cases of nail EB manifesting in adolescence or early adulthood may occur. In rare cases, nail abnormalities may precede skin blistering, as in late-onset JEB and in the pretibial variant of localized DEB [64].
Nail abnormalities can even be an isolated finding, as in the acral "nails only" subtype of localized dominant dystrophic epidermolysis bullosa (DDEB), in which the involvement is often limited to the toenails and can be mild and easily overlooked [65].
An overview of the management of EB is provided separately. (See "Overview of the management of epidermolysis bullosa".)
Pachyonychia congenita — Pachyonychia congenita is a rare, autosomal dominant disorder of keratinization caused by variants in KRT6A, KRT6B, KRT6C, KRT16, or KRT17, with defective keratinization characterized by a constellation of clinical features, including characteristic, hypertrophic nail dystrophy; painful, palmoplantar blisters; cutaneous cysts; follicular hyperkeratosis; and oral leukokeratosis [66].
Nail and skin changes are present at birth in approximately 50 percent of cases, but by the age of five years, they are evident in more than 75 percent of children. Nail alterations involve all 20 nails and are characterized by marked nail thickening with increased curvature due to nail bed hyperkeratosis (picture 12A-B). By the age of 10 years, severe pain associated with palmoplantar keratoderma is a common symptom and greatly impairs quality of life [67].
The pathogenesis, classification, clinical features, diagnosis, and management of pachyonychia congenita are discussed in detail separately. (See "Pachyonychia congenita".)
Dyskeratosis congenita — Dyskeratosis congenita (DC) is a rare, inherited disorder caused by variants in genes that maintain telomere length in rapidly dividing cells, resulting in premature cell death, senescence, or genomic instability in many organs and tissues [68]. It is clinically characterized by mucocutaneous abnormalities, bone marrow failure, and a predisposition to cancer (table 2).
The triad of nail dystrophy; leukokeratosis of the oral mucosa; and extensive, net-like pigmentation of the skin is typical of DC (picture 13) [69]. Nail changes are early manifestations of DC, appearing during early childhood (sometimes in the first year of life), and include nail thinning with longitudinal splitting, ridging, and atrophy (picture 14A-B). Fingernails are more severely affected than toenails. The onychoscopic features of DC include parallel longitudinal ridges and deep furrows, jagged distal edges, and splinter hemorrhages (picture 15) [70].
The pathogenesis, clinical features, diagnosis, and management of DC are discussed in detail separately. (See "Dyskeratosis congenita and other telomere biology disorders".)
SUMMARY
●The nail unit in newborns and infants – In healthy newborns, the fingernails are oval or rectangular in shape, with a longitudinal major axis, and are flat in most cases. The index fingernail measures approximately 5 mm in length and 3.5 mm in width, and the thumbnail is approximately 9 to 10 mm in width. (See 'Anatomy of the nail unit in newborns and infants' above.)
●Physiologic, transitory changes – Physiologic nail changes in newborns and infants include koilonychia (spoon nails (picture 1)); transient, melanic pigmentation of the proximal nail fold (common in newborns with highly pigmented skin); Beau (transverse) lines of the fingernails (picture 2); transient onychoschizia (lamellar splitting of the free edge of the nail plate); and congenital hypertrophy of the great toenail's lateral nail folds (picture 3). (See 'Physiologic (transitory) nail changes in newborns and infants' above.)
●Nonsyndromic nail disorders – Many isolated, nonsyndromic congenital nail disorders have been described. For most of them, the underlying genetic alteration and pattern of inheritance are unknown. Among them, well-characterized disorders include twenty-nail dystrophy (nonsyndromic congenital nail disorder 1; MIM #161050), hereditary leukonychia (porcelain nails; MIM #151600), congenital malalignment of the great toenail, and racket thumbs. (See 'Nonsyndromic congenital nail disorders' above.)
●Syndromic nail disorders – Several multiple malformation syndromes are associated with nail hypoplasia (anonychia [absence of nails] or micronychia [nails that are smaller than normal]). These include Cook syndrome, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures) syndrome (MIM #220500), Coffin-Siris syndrome, focal dermal hypoplasia (Goltz syndrome; MIM #305600), nail-patella syndrome, and ectodermal dysplasias. (See 'Syndromes with associated anonychia/micronychia' above.)
Syndromes associated with nail dystrophy and/or hyperkeratosis include pachyonychia congenita (picture 12A), epidermolysis bullosa (EB), especially junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB), and dyskeratosis congenita (DC). (See 'Syndromes associated with nail dystrophy or hyperkeratosis' above.)
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