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 keratosis pilaris mainly on the occiput. The hair of this 4-year-old boy was never cut. 
Monilethrix that affects the entire scalp. 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.
Autosomal dominant monilethrix is caused by mutations in hair keratin genes KRT81, KRT83, or KRT86, whereas the autosomal recessive form results from mutations in the desmoglein 4 gene (DSG4).[11] Compound heterozygous mutations in the DSG4 gene may occur.
Epidemiology
Frequency
United States
No data are available.
International
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.
Zlotogorski A, Marek D, Horev L, Abu A, Ben-Amitai D, Gerad L, et al. An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis. J Invest Dermatol. Jun 2006;126(6):1292-6. [Medline].
Korge BP, Hamm H, Jury CS, Traupe H, Irvine AD, Healy E, et al. Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype. J Invest Dermatol. Oct 1999;113(4):607-12. [Medline].
Winter H, Vabres P, Larregue M, Rogers MA, Schweizer J. A novel missense mutation, A118E, in the helix initiation motif of the type II hair cortex keratin hHb6, causing monilethrix. Hum Hered. Sep-Oct 2000;50(5):322-4. [Medline].
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van Steensel MA, Steijlen PM, Bladergroen RS, Vermeer M, van Geel M. A missense mutation in the type II hair keratin hHb3 is associated with monilethrix. J Med Genet. Mar 2005;42(3):e19. [Medline].
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Khandpur S, Bairwa NK, Reddy BS, Bamezai R. A study of phenotypic correlation with the genotypic status of HTM regions of KRTHB6 and KRTHB1 genes in monilethrix families of Indian origin. Ann Genet. Jan-Mar 2004;47(1):77-84. [Medline].
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