Why Is This Child’s Hair Not Growing?

A 2-year-old Caucasian girl presented with diffuse thin hair on the scalp since birth. She was born to a 30-year-old gravida 3 para 2 mother at 38 weeks of gestation following an uncomplicated pregnancy and an unremarkable vaginal delivery. Her parents were nonconsanguinous, and there was no family history of hair disorders. The parents remarked that the child’s hair remained short and was not growing. The child had never required a haircut, and there was no history of self plucking, pulling, or twisting of the hair. The parents also noted that even gentle traction on the child’s hair resulted in her hair loss without pain or discomfort. The child’s growth and developmental milestones were normal, and she was otherwise in good health and was not taking any medications or over-the-counter supplements. Aggravating factors were denied, and the child’s diet was healthy.

On examination, the child was alert and not in distress. Her scalp hair was sparse, thin, fine, short, and blonde. An area of frizzy, kinked, and uncombable hair was present in the occipital area. There were no patches of complete alopecia or hair broken off at the scalp. 

The scalp surface was unremarkable and did not have erythema, papules, pustules, crust, scale, or scarring. The girl’s eyelash and eyebrow hair were normal in appearance and density, and the rest of the examination results were unremarkable. In particular, there were no abnormalities of her skin, nails, teeth, or eyes, as well as no cervical lymphadenopathy or systemic abnormalities.

The hair pull test was positive with at least 10 hairs being easily and painlessly extracted with each gentle pull at all sites of the scalp. Hair trichogram showed that most of the epilated hairs proved to be dystrophic anagen hairs, with distorted, bent bulbs resembling mouse-tail appearance, abnormally keratinized inner root sheaths, absent outer root sheaths, and ruffled cuticles with characteristic floppy sock appearance. 

What’s your diagnosis?

Answer: Loose anagen syndrome

LOOSE ANAGEN SYNDROME: AN OVERVIEW 

Based on the examination and hair pull test, a diagnosis of loose anagen syndrome was made. The parents were reassured of the benign nature of the condition and that it would likely improve with time. Loose anagen syndrome, also known as loose anagen hair syndrome, is characterized by loose anchoring of anagen hairs that can be easily and painlessly plucked from the scalp.¹ The condition was first described in 1984 by Zaun at the First Congress of the European Society for Pediatric Dermatology (Munster, Germany, October 4 to 7, 1984). Zaun termed the entity “syndrome of loosely attached hair in childhood.”² The term “loose anagen syndrome” was coined by Price and Gummer in 1989.³

EPIDEMIOLOGY

The incidence of loose anagen syndrome is estimated at 2 to 2.5 cases per million per year,^4-6 with a female to male ratio of approximately 6:1.^7-9 Loose anagen syndrome is more commonly observed in white populations with blonde hair than in other ethnic groups.^3-5,10 The disease typically affects children between 2 and 8 years of age.^6,11 Adult cases have been described, mostly in parents of affected children.⁹ Boys and children with dark hair may also be affected.^1,8 Most cases are sporadic,^5,12 but the condition can also be inherited as an autosomal disorder with incomplete penetrance.^12-14 

ETIOPATHOGENESIS 

The exact etiopathogenesis is not known. It is believed that the condition results from premature and irregular keratinization of the inner root sheath leading to an impaired adhesion between the cuticle of the inner root sheath and the cuticle of the hair shaft.^9,15,16 Mutations in the gene encoding for the companion layer keratin (K6HF) or a defect in the gene encoding for keratin (K6IRS), which is specific for the inner root sheath of the hair follicle, account for at least some of the cases.^4,12,15,17 Mutations in SHOC2 and PPP1CB have been reported in patients with Noonan syndrome with loose anagen hair.¹⁸

HISTOPATHOLOGY

Histologic findings include clefting between inner root sheath, inner root sheath and outer root sheath, outer root sheath and fibrous sheath, vacuolization and intercellular edema in the prekeratinized Huxley cell zone, and dyskeratotic changes of Henle cells and cuticle cells of both the inner root sheath and hair shaft.^16,17

Light microscopy of epilated hairs shows predominance of anagen hairs with abnormally keratinized inner root sheaths, separation of the hair cuticle from the inner root sheath, ruffling or rippling of the cuticle on the proximal hair shaft with a floppy or rumpled sock appearance, and pigmented and deformed hair bulbs that may appear long, tapered, twisted, or positioned at an acute angle to the long axis of the hair shaft with a mouse-tail or hockey-stick–like appearance.^6,15

CLINICAL MANIFESTATIONS

The typical patient is a Caucasian girl with short, sparse, thin, fine, lusterless, unruly, blonde hair that does not grow long and seldom requires cutting.^9,11 The affected individual usually has diffuse or, much less commonly, patchy alopecia.¹⁹ Hair is often easily knotted at the occiput, presumably as a result of repeated rubbing of the occipital area against the pillow at night.^10,12 The hair is also reported as dry, rough, sticky, tacky, or matted.^13,20 The hair can be easily and painlessly removed from the scalp with a gentle pull using a thumb and forefinger. Typically, the hairs are not fragile or breakable.^15,19 Characteristically, the scalp is unremarkable in appearance, without inflammation or scarring.

Three phenotypes have been recognized on the basis of the predominance of the 3 most important clinical signs, namely, reduced hair length, altered hair texture, and increased hair shedding. Each of the phenotypes have in common the finding of easily and painlessly extracted loose anagen hairs on gentle hair pull.^9,14,17,21 These phenotypes are: type A, characterized by diffusely thin and sparse hair that does not grow long; type B, characterized by mainly unruly hair; and type C, characterized by normal-appearing hair with excessive shedding of loose anagen hairs.²¹ The above phenotypes appear to be age-dependent, with types A and B phenotypes almost exclusively affecting children, and type C predominately affecting adults.¹⁵ There is a tendency for types A and B phenotypes to evolve into type C with age.^15,17

Loose anagen syndrome is usually restricted to scalp hair.¹⁹ Occasionally, the eyebrows, eyelashes, and body hair may also be involved.^13,19 In most cases, loose anagen syndrome is isolated. Occasionally, it can occur in association with developmental or ectodermal abnormalities such as ocular coloboma, woolly hair, alopecia areata, Noonan syndrome, hypohidrotic ectodermal dysplasia, EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome, nail-patella syndrome, trichorhinophalangeal syndrome, and FG syndrome (also known as Opitz-Kaveggia syndrome).^9,13,16,17

Diagnosis 

Loose anagen syndrome should be suspected in an individual with sparse and thin hair that seldom requires cutting; the typical patient is a Caucasian girl with blonde hair between 2 and 8 years of age. Painless extraction of at least 10 loose anagen hairs by pull test and the presence of more than 70% loose anagen hair on trichogram have been proposed as diagnostic criteria.^9,22 

DIFFERENTIAL DIAGNOSIS

Differential diagnosis includes short anagen syndrome, uncombable hair syndrome, telogen effluvium, anagen effluvium, alopecia areata, trichotillomania, and tinea capitis. Short anagen syndrome is characterized by the inability to grow long hair and an increase in the number of hairs in telogen due to a decreased duration of the anagen phase.²² Uncombable hair syndrome is characterized by dry, light-colored, spangled hair that sticks out from the scalp and cannot be made to lie flat, giving rise to a “spun-glass” appearance.⁶ Telogen effluvium refers to the loss of an abnormally large quantity of telogen hairs (the tip is devoid of color and white) following the premature, synchronous, and abrupt conversion of hair follicle from the anagen phase to the telogen phase.²³ 

Common precipitating factors include severe infection, chronic illness, and psychologic stress.²³ Anagen effluvium most often follows chemotherapy; the affected hairs are dystrophic with tapered proximal ends.¹² Alopecia areata most commonly manifests as sudden loss of hair in a well-demarcated, localized area in the scalp, although diffuse alopecia areata exists.²⁴ The lesion is usually round or oval. “Exclamation point hairs” are frequently seen at the periphery of the lesion.²⁴ 

Trichotillomania is an intriguing compulsive disorder characterized by uncontrollable, self-inflicted hair pulling or twisting and tugging resulting in noticeable hair loss.²³ Clinically, the affected area has hairs of different lengths, some with blunt ends (broken hairs) and some with tapered ends (new growth).²³ Some hairs may be broken mid-shaft and appear as uneven stubble, whereas others appear as small black dots on the surface of the scalp. A pull test is negative. Approximately 70% to 90% of cases occur in females. Tinea capitis often presents as fine scaling with patches of circular alopecia; diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff; or patches of well-demarcated areas of alopecia with fine scale, studded with broken-off, swollen hair stubs, resulting in a “black dot” appearance. 

Complications

The condition is cosmetically unsightly and may have an adverse effect on the quality of life.¹² This may in turn lead to parental anxiety. 

PROGNOSIS

The prognosis is favorable. The hair usually grows progressively longer, denser, and darker in color with increasing age, particularly after puberty.^1,10 There is persistence of the defect of hair shaft anchorage, though to a lesser degree.^3,9

MANAGEMENT 

As the condition is benign and self-limited, no treatment is necessary apart from reassurance and watchful observation. Minoxidil may hasten resolution and may be considered in severe cases.^5,17 Presumably, minoxidil works by increasing local cutaneous blood supply, prolonging the anagen phase, and enhancing cell proliferation and DNA synthesis in follicular and perifollicular keratinocytes.^5,17 

Alexander K.C. Leung, MD, is a clinical professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Benjamin Barankin, MD, is medical director and founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.

REFERENCES 

1. Agi C, Cohen B. A case of loose anagen syndrome in an African American girl. Pediatr Dermatol. 2015;32(3):e128-e129.

2. Zaun H. Syndrome of loosely attached hair in childhood. In: Happle R, Grosshans E, eds. Pediatric Dermatology: Advances in Diagnosis and Treatment. New York, NY: Springer Verlag NY Inc; 1984:64-65.

3. Price VH, Gummer CL. Loose anagen syndrome. J Am Acad Dermatol. 1989;20(2 Pt 1):249-256.

4. Avhad G, Ghuge P, Jerajani H. Loose anagen hair syndrome. Indian Dermatol Online J. 2014;5(4):548-549.

5. Chandran NS, Oranje AP. Minoxidil 5% solution for topical treatment of loose anagen hair syndrome. Pediatr Dermatol. 2014;31(3):389-390.

6. Lee AJ, Maino KL, Cohen B, Sperling L. A girl with loose anagen hair syndrome and uncombable, spun-glass hair. Pediatr Dermatol. 2005;22(3):230-233.

7. Kanwar AJ, Narang T. Anagen effluvium. Indian J Dermatol Venereol Leprol. 2013;79(5):604-612. 

8. Pham CM, Krejci-Manwaring J. Loose anagen hair syndrome: an underdiagnosed condition in males. Pediatr Dermatol. 2010;27(4):408-409.

9. Tosti A. Loose anagen hair syndrome and loose anagen hair. Arch Dermatol. 2002;138(4):521-522.

10. Swink SM, Castelo-Soccio L. Loose anagen syndrome: a retrospective chart review of 37 cases. Pediatr Dermatol. 2016;33(5):507-510. 

11. Srinivas S. Loose anagen hair syndrome. Int J Trichology. 2015;7(3):138-139.

12. Abdel-Raouf H, El-Din WH, Awad SS, et al. Loose anagen hair syndrome in children of Upper Egypt. J Cosmet Dermatol. 2009;8:103-107.

13. Cantatore-Francis JL, Orlow SJ. Practical guidelines for evaluation of loose anagen hair syndrome. Arch Dermatol. 2009;145(10):1123-1128.

14. Chong AH, Sinclair R. Loose anagen syndrome: a prospective study of three families. Australas J Dermatol. 2002;43(2):120-124.

15. Dey V, Thawani M. Loose anagen hair syndrome in black-haired Indian children. Pediatr Dermatol. 2013;30(5):579-583.

16. Mirmirani P, Uno H, Price VH. Abnormal inner root sheath of the hair follicle in the loose anagen hair syndrome: an ultrastructural study. J Am Acad Dermatol. 2011;64(1):129-134.

17. Dhurat RP, Deshpande DJ. Loose anagen hair syndrome. Int J Trichology. 2010;2(2):96-100.

18. Gripp KW, Aldinger KA, Bennett JT, et al. A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair. Am J Med Genet A. 2016;170(9):2237-2247.

19. Santiago F, Vieira R, Figueiredo A. Loose anagen hair syndrome: an unusual cause of alopecia of cosmetic importance only. J Cosmet Dermatol. 2009;8(3):226-227.

20. Chapalain V, Winter H, Langbein L, et al. Is the loose anagen hair syndrome a keratin disorder? A clinical and molecular study. Arch Dermatol. 2002;138(4):501-506.

21. Olsen EA, Bettencourt MS, Cote NL. The presence of loose anagen hairs obtained by hair pull in the normal population. J Investig Dermatol Symp Proc. 1994;4(3):258-260.

22. Avashia N, Woolery-Lloyd H, Tosti A, Romanelli P. Short anagen syndrome in an American woman. J Am Acad Dermatol. 2010;63(6):1092-1093.

23. Leung AK, Robson WL. Hair loss in children. J Roy Soc Health. 1993;113:252-256.

24. Hon KL, Leung AK. Alopecia areata. Recent Pat Inflamm Allergy Drug Discov. 2011;5(2):98-107.