|KRT81 (602135), KRT83 (602765), KRT86 (601928)
Monilethrix is a genetic disorder of hair keratins with a structural defect of the hair shaft, resulting in short, fragile, broken hair that appears beaded (beads on a string). The term monilethrix derives from the Latin word for necklace (monile) and the Greek word for hair (thrix).1 Autosomal dominant mutations in the hair-keratins KRT81, KRT83 and KRT86 (all 12q13.13) are causative in most cases.2 Further, an autosomal recessive form has been described due to mutations in the desmoglein 4 gene (DSG4).3
Onset of the disease is during the first few months of life. Affected individuals develop fragile hair that tends to fracture, especially on areas prone to friction (e.g. occipital, top of the head, retroauricular). As a consequence, patients show varying degrees of dystrophic alopecia. In the mildest forms, only the occipital regions of the scalp are involved or solely slight fraying occurs. Severe forms show involvement of secondary sexual hair, eyebrows and sometimes eyelashes. Patients may also display follicular hyperkeratosis on the scalp, nape of the neck, and extensor surfaces of the upper arm and thigh or perifollicular erythema. Nail dystrophy has been reported. The condition generally improves during puberty and pregnancy, but it never disappears completely.1, 3-5
The hair follicle is a rather complex structure. From the outside to the inside it is built up by an outer root sheet, the companion layer, the inner root sheet and the hair fiber. Except for the companion layer, each entity is further subdivided into differentiated layers. The affected hair keratins in monilethrix, KRT81, KRT83, KRT86, are expressed in the cortex of the hair fiber (mutations affect the helix termination motif of hair-keratins). This explains the dystrophic constrictions of hairs in monilethrix (lacking the medulla) that are regularly separated by elliptical nodes of normal thickness, although the exact underlying mechanisms are still not clear. The fibers easily break at the thin internodal regions, which leads to alopecia.6, 7
Clinical history and physical examination is the basis for diagnosis. Trichoscopy may confirm the diagnosis by showing elliptical nodes of normal thickness on the hair shafts that are regularly separated by dystrophic constrictions / internodes.8 Molecular genetic analysis should include KRT81, KRT83, KRT86 and DSG4.
Differential diagnosis include hypotrichosis simplex, which is caused by mutations in DSG4 and has clinical overlap with monilethrix. Pseudomonilethrix also presents with alopecia, but it can be distinguished by the absence of constrictions in the hair fiber; instead it shows flattened, irregular beading.
No satisfying treatment is currently available. Avoidance of mechanical stress, such as extensive combing, hair dressing trauma and brushing is recommended. Depilation only achieves regrowth of normal looking hair for a short while. The use of griseofulvin, zinc-sulfate, X-ray depilation, and topical application of retinoic acid has shown temporary improvement. The same has been reported with the application of minoxidil and tretinoin, and with the administration of etretinate. Oral minoxidil in a low-dose has shown efficacy in two women for at least 6 months.9, 10
3. Zlotogorski A, Marek D, Horev 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. 2006;126(6):1292-1296.