Monilethrix

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Updated: Jun 21, 2016
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
Overview

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.

Lusterless, dry, brittle hair with alopecia and ke Lusterless, dry, brittle hair with alopecia and keratosis pilaris mainly on the occiput. The hair of this 4-year-old boy was never cut.
Monilethrix that affects the entire scalp. 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]

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. [6] A mutational hotspot may exist in the helix termination motif of hHb6. [7] A missense mutation in the type II hair keratin hHb3 has been shown to be associated with monilethrix. [8] 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. [9] 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. [10]

An autosomal recessive form of monilethrix was found to be caused by mutations in 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 4 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. [11] A novel D323G mutation of the DSG4 gene was evident in a child with localized autosomal recessive hypotrichosis overlapped with monilethrix. [12]

Autosomal dominant monilethrix is caused by mutations in hair keratin genes KRT81, KRT83, or KRT86, [13] whereas the autosomal recessive form results from mutations in the desmoglein 4 gene (DSG4). [14] 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. [15]

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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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