DISEASE CARD

Disease group Keratinization disorders
DISEASE NAME MONILETHRIX
Synonymous Monilitrichie
Estimated prevalence Unknown
OMIM 158000
Inheritance Autosomal dominant
Gene (s) KRT81 (602135), KRT83 (602765), KRT86 (601928)

Definition

Monilethrix is a genetic disorder of hair keratins that results in a structural defect of the hair shaft. The disease results 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].

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. Monilethrix is caused by mutations in either one of the hair-keratins KRT81, KRT83 and KRT86 (all 12q13.13), which are expressed in the cortex of the hair fiber [2].

Besides the keratin-based form of monilethrix, which is inherited in an autosomal dominant fashion, an autosomal recessive form has been described, which is caused by mutations in the desmoglein 4 gene (DSG4) [3].

Clinical description

Onset of the disease is during the first few months of life. Affected individuals develop fragile hair that tends to fracture. As a consequence, patients show varying degrees of dystrophic alopecia. In the mildest forms, only the occipital regions of the scalp are involved; severe forms include secondary sexual hair, eyebrows and sometimes eyelashes. Patients also show follicular hyperkeratosis on the scalp, nape of the neck, and extensor surfaces of the upper arm and thigh. Perifollicular erythema may also appear. Nail dystrophy has been reported. The condition generally improves during puberty and pregnancy, but it never disappears completely [1, 3].

Pathogenesis

Hair fibers show dystrophic constrictions regularly separated by elliptical nodes of normal thickness. The fibers easily break at the thin internodal regions, which leads to alopecia. On the molecular level, mutations were shown to affect the helix termination motif of hair-keratins [4, 5].

Diagnosis

Under the light microscope, hair fibers show elliptical nodes of normal thickness that are regularly separated by dystrophic constrictions. Molecular genetic analysis should include KRT81, KRT83, KRT86 and DSG4.

Differential diagnosis should 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.

Treatment

No satisfying treatment is currently available. Avoidance of mechanical action, such as combing 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 [6].

References

1
Schweizer J. (2006) More than one gene involved in monilethrix: intracellular but also extracellular players. J Invest Dermatol 126:1216-1220.

2
Moll R, Divo M, Langbein L. (2008) The human keratins: biology and pathology. Histochem Cell Biol 129:705-733.

3
Zlotogorski A, Marek D, Horev L, Abu A, Ben-Amitai D, Gerad L, Ingber A, Frydman M, Reznik-Wolf H, Vardy DA, Pras E. (2006) An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis. J Invest Dermatol 126:1292-1296.

4
Winter H, Rogers MA, Langbein L, Stevens HP, Leigh IM, Labrèze C, Roul S, Taieb A, Krieg T, Schweizer J. (1997) Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix. Nat Genet 16:372-374.

5
Winter H, Rogers MA, Gebhardt M, Wollina U, Boxall L, Chitayat D, Babul-Hirji R, Stevens HP, Zlotogorski A, Schweizer J. (1997) A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix. Hum Genet 101:165-169.

6
Information retrieved from Orphanet:
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=573 Pr Francisco CAMACHO-MARTÍNEZ. Last updated May 2012.