Monilethrix

Background

Monilethrix is an autosomal dominant disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The phenotype results in hair fragility and patchy dystrophic alopecia. The term monilethrix is derived from monile (Latin), which means necklace, and thrix (Greek), which means hair. This term indicates the resemblance of the hair to a string of beads or a necklace. Monilethrix is also known as nodose hair.

In 1897, Walter Smith first described monilethrix (pili moniliformes [Latin]). Regular nodes and internodes that lead to breakage of the hair and varying degrees of alopecia characterize this hair-shaft anomaly. Monilethrix is inherited as an autosomal dominant trait with high penetrance but variable expressivity. However, autosomal recessive inheritance for this disease has been sporadically reported.^[1] Note the images below.

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Lusterless, dry, brittle hair with alopecia and keratosis pilaris mainly on the occiput. The hair of this 4-year-old boy was never cut.

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Monilethrix that affects the entire scalp.

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Pathophysiology

The etiology of monilethrix remains obscure. Results of genetic linkage analysis suggest that monilethrix is likely caused by a mutation in a hair keratin. Mutations in the human hair basic keratins hHb1 and hHb6 have been described with this disorder.^{[2, 3]} The most frequent mutation is the E413K mutation in hHb6.^[4] In a study of a large family from Turkey with 11 affected members, the mutation (E402K) in exon 7 of the KRT86 gene was identified as etiologic.^[5] A rare mutation in the KRT86 gene was described in monozygotic twins in Poland.^[6]

These mutations in the helix-encoding region in the hair-specific keratins hHb1 and hHb6 may represent different novel heterozygous point mutations of the same codon in exon 7 of the hHb6 gene.^[7] A mutational hotspot may exist in the helix termination motif of hHb6.^[8] A missense mutation in the type II hair keratin hHb3 has been shown to be associated with monilethrix.^[9] Analysis for gene mutation in a Chinese mother and her daughter with monilethrix revealed heterozygous transition of c.1204G to A (p.E402K) of hHB6 and demonstrated that affected family members carried the p.E402K mutation.^[10] Twenty-one affected individuals in 2 unrelated monilethrix families of Indian origin were studied, and a point mutation (g.4624G>A) in the HTM motif (exon-7) of the KRTHB6 gene was found in all the affected members, leading to E413K change in this basic keratin.^[11]

An autosomal recessive form of monilethrix was found to be caused by mutations in the desmoglein 4 gene (DSG4) while evaluating 12 Jewish families from Iraq, Iran, and Morocco, with microscopic findings of monilethrix, but with no evidence of vertical transmission.^[1] Sequencing of the main candidate gene from this region revealed four different mutations in desmoglein 4 (DSG4). To date, whether monilethrix is a disorder of the function or structure of the hair has not been determined. Recent data imply that the pathogenesis of monilethrix is related to dysfunctional mutated DSG4 undergoing degradation, with unfolded protein response induction.^[12] A novel D323G mutation of the DSG4 gene was evident in a child with localized autosomal recessive hypotrichosis overlapped with monilethrix.^[13]

Autosomal dominant monilethrix is caused by mutations in hair keratin genes KRT81, KRT83, or KRT86,^[14] whereas the autosomal recessive form results from mutations in DSG4.^[15] Compound heterozygous mutations in the DSG4 gene may occur.

Congenital monilethrix and hereditary unilateral external auditory canal atresia were found to be co-inherited in a Chinese pedigree with recurrent KRT86 mutation.^[16] A novel missense KRT86 mutation was documented in a Chinese family with monilethrix.^[17]

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Epidemiology

Frequency

No data are available.

Race

No racial predilection is evident for monilethrix. Monilethrix is not linked to any particular hair color.

Sex

No sex limitation is evident for monilethrix.

Age

The onset of monilethrix is during infancy.

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Prognosis

Monilethrix is a lifelong disease. Symptoms spontaneously regress during puberty and pregnancy, but the condition never disappears completely.

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History

Monilethrix is a lifelong disease. Internodal fragility leads to breakage of hair and varying degrees of alopecia. Symptoms spontaneously regress during puberty and pregnancy, but the condition never disappears completely. Affected persons are generally healthy. They may report sparse and brittle hair since early childhood.^[18]

Keratosis pilaris is almost invariably associated with monilethrix. Sites of predilection are the scalp, nape of the neck, and extensor surfaces of the upper arm and thigh. No evidence suggests that keratosis pilaris can lead to the formation of beaded hair. Koilonychia is commonly associated with monilethrix. A wide variety of concomitant ectodermal defects are reported in the literature. Examples include dental abnormalities, juvenile cataracts, and some neurologic defects that appear as a cognitive deficiency or epilepsy.

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Physical Examination

Lanugo hair usually appears normal at birth. Several months later, it is replaced by moniliform hair, which is dry, brittle, fragile, and lusterless. The hair breaks spontaneously to 0.5-2.5 cm. Broken short hair looks as if it has been burnt.

Monilethrix occurs mainly on the scalp, predominantly on the occiput and nape and occasionally on other scalp areas. Scalp involvement can be widespread or circumscribed. The eyelashes, eyebrows, pubic, axillary, and limb hair are occasionally involved.

Monilethrix is associated with follicular keratosis (horny follicular papules). Patients with monilethrix and a prolonged clinical course of several years' duration may have cutaneous atrophy (aplasia pilorum moniliformes [Latin]).

The absence of macroscopic beading should prompt repeated hair microscopy and not an automatic rejection of this diagnosis.^[19] Dermatoscopy can be helping in making the diagnosis, especially with adequate hair sampling. It shows zones of dystrophic constriction of the hair shaft, separated at regular intervals by elliptical nodes of normal thickness, producing a "necklace" appearance.^{[18, 20]}

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Other Tests

Light microscopy, with macroscopic examination, aids in diagnosis. The hair shaft has regular, elliptical, fusiform, or spindle-shaped swellings (nodes) that are 0.7-1.0 mm in diameter and separated by constricted internodes. The nodes have the diameter of normal hair and are medullated, whereas the internodes have no medulla and are the sites of fracture. Pigment is present in both segments.

Scanning electron microscopy may reveal useful findings. All nodes demonstrate normal or worn transverse cuticular scales. Internodes show a dense longitudinal pattern of scales and ridging.

Dermoscopy can be used as a tool for rapid diagnosis of monilethrix.^{[23, 24, 25]} It may show hair shafts with uniform elliptical nodes and intermittent constrictions, hairs bent regularly at multiple locations, and a tendency to fracture at constriction sites. The hair may be of varying lengths, with multiple shafts broken.^[26] Hair with normal morphology may be interspersed within beaded hair. Scalp hair may have white dots and a honeycomb pigment network. The forearm hair may appear to be normal but, with dermoscopy, beaded short hairs may be evident. Videodermoscopy of hair (trichoscopy) may be similarly used.^[27]

Note the images below.

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Photomicrograph shows the regular nodes and internodes of the hair shaft in monilethrix, or pili moniliformes (original magnification X200).

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Photomicrograph shows the regular nodes and internodes of the hair shaft in monilethrix, or pili moniliformes (original magnification X200).

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Histologic Findings

Landau et al recently described an easy way to diagnose severe neonatal monilethrix.^[28] One can scrape the scalp with a glass slide, collect epidermal cells and rudimentary hair fragments, and examine the unstained specimen by using a microscope. One should find single or paired beads of typical monilethrix hair.

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Medical Care

No effective treatment is available.^{[29, 30]} A wig can be used. Some report spontaneous improvement.

The systemic administration of vitamins, retinoids, griseofulvin, oral contraceptives, steroids, radiation therapy and external desquamative ointments, steroid preparations, and minoxidil does not show impressive results. A 7-year-old girl treated with oral acitretin had good clinical and cosmetic results, but clinical symptoms recurred after discontinuation of acitretin therapy.^[31]

The avoidance of trauma is the most effective method of managing this anomaly. Congenitally abnormal hair tends to have an increased susceptibility to weathering and cosmetic damage (eg, sunlight exposure, dyeing, bleaching, perming, curling), which can prevent hair from growing to its maximum length.

No definitive therapy is recognized, but topical minoxidil 2% (1 mL night and day for 1 y) led to an increase of normal hair shaft without any adverse effects in one report. Topical minoxidil 2% may be a good therapeutic option to treat monilethrix,^[32] although its use in children may require enhanced monitoring.^[33]

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Prevention

The avoidance of trauma is the most effective method of managing this anomaly. Because congenitally abnormal hair tends to have an increased susceptibility to weathering and cosmetic damage, patients should avoid exposing their hair to the following:

• Sunlight
• Dyes
• Bleaches
• Chemicals used in permanent waving
• Curling devices

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