Usefulness of Trichoscopy over Hair Light Microscopy in Menkes Disease

Abstract

Menkes disease (MD) is a rare X-linked recessive neurodegenerative disorder caused by mutations in the ATP7A gene, with a high mortality rate within the first 3 years of life. It typically affects males and is characterized by impaired copper distribution and malfunction of several copper-dependent enzymes. Patients develop progressive muscle hypotonia associated with neurological damage and hair shaft dysplasia − particularly pili torti. Pili torti is usually very subtle in the first 3 months of life and gradually increases during the first year. Light microscopy examination in search for pili torti requires the observation of more than 50 hair shafts. In contrast, trichoscopy with a hand-held dermatoscope allows to easily identify the hair shaft defect. We report a case of a Hispanic male infant with MD in whom we show that trichoscopy is superior to hair light microscopy in revealing pili torti.

Established Facts

• Scalp hair in Menkes disease (MD) becomes kinky, coarse, sparse, brittle, and hypopigmented by 2–3 months of age.

• Pili torti is the main hair shaft defect observed in patients with MD.

Novel Insights

• Trichoscopy is superior to light microscopy in revealing pili torti in Menkes disease.

Introduction/Literature Review

Menkes disease (MD) is a lethal X-linked disorder of copper metabolism with multisystemic involvement. This disease shows wide variability and clinical heterogeneity, ranging from a severe clinical course leading to death in early childhood to a milder form termed occipital horn syndrome (OHS) with connective tissue abnormalities and longer survival. Patients affected by MD present with progressive muscle hypotonia associated with neurological damage and hair shaft dysplasia [1].

The scalp hair may appear normal at birth, but by 2–3 months of age becomes kinky, coarse, sparse, brittle, and hypopigmented [2]. Several hair shaft abnormalities such as pili torti (flattened shaft twisted on its own axis) being the more common, trichorrhexis nodosa (transverse fracture expanded by wide separation and fraying of hair fibers), monilethrix (intermittent narrowing of the hair shaft), trichoclasis (transversal splinted by a partially intact cuticle), and trichoptilosis (longitudinal splitting of the hair shaft) have been described in patients with MD [2, 3].

Light microscopy examination of the hair shaft has long been used to reveal hair shaft dysplasia and even aids in the diagnosis of milder forms of MD [4]. However, trichoscopy may show the characteristic light microscopy features with no need of plucking or cutting hairs for diagnostic purposes [5]. Herein, we report a case of a Hispanic male infant with MD in whom we show that trichoscopy is superior to hair light microscopy in revealing the classic hair shaft defect.

Case Report/Case Presentation

A 14-month-old Hispanic male born from nonconsanguineous parents was admitted to our institute with generalized hypotonia, poor head control, and regression of achieved milestones. Pregnancy was uneventful and he was born at 36 weeks gestation with a normal birth weight for his age. At 3 months of age, a right inguinal herniorraphy and an orchidopexy were performed. At the age of 6 months, the mother noticed frank developmental delay.

On clinical examination, the patient presented short palpebral fissures, exotropia of both eyes, and prominent cheeks. Neck was short, and fingers were fusiform. Dermatologic examination revealed lax and very light-colored skin, and scalp hair was hypopigmented, brittle, short, and sparse, with a kinky appearance. Hair shafts easily fractured resulting in severe alopecia, mainly in the occipital region (shown in Fig. 1).

Fig. 1.

Severe alopecia in the occipital region. Hair was hypopigmented, brittle, short, and sparse, with a kinky appearance.

The pediatric neurologist suspected MD and ordered serum ceruloplasmin levels which were low (0.05 ng/dL; normal level 0.2–0.6 ng/dL). Serum copper levels were not available. Hair shafts were analyzed under light microscopy and only scarce twists were observed (shown in Fig. 2a) in contrast with trichoscopy which revealed several flattened hair shafts twisted 180° along their axis at irregular intervals in approximately 50% of the sampled hairs (shown in Fig. 2b), features of pili torti characteristic of MD. The molecular study detected a mutation on the ATP7A gene confirming the diagnosis. The patient has been treated with oral copper histidinate, and so far has had partial improvement in hair pigmentation and muscle tone, however neurodevelopmental arrest persists.

Fig. 2.

a Hair light microscopy showing one hair shaft with scarce twists. b Trichoscopy reveals hair shafts with 180° twisting over their own axis (pili torti) in approximately 50% of the examined hairs.

Discussion/Conclusion

MD is a rare neurodegenerative X-linked recessive disorder, leading to death within a few years. It almost exclusively affects males, while heterozygous females tend to be carriers due to skewed inactivation of X chromosome [2]. It is caused by mutations of the ATP7A gene, responsible for encoding the copper-transporting protein ATP enzyme − necessary for the distribution and metabolism of copper in tissues, leading to malfunction of several copper-dependent enzymes [6].

The degree to which residual ATP7A function is maintained, depending on the type of mutation, determines the severity of the clinical phenotypes, resulting in classic MD, intermediate phenotypes, and OHS. Classical MD is the most severe form and patients usually die before the third year of life, in contrast to the OHS, which is the mildest form [2, 7].

Patients appear normal at birth and suddenly develop neurologic deterioration, seizures, lethargy, vomiting, diarrhea, and loss of milestones from about 2 to 3 months of age. Muscle tone is decreased in early life, but is later replaced by spasticity and weakness of the extremities. The patients are usually diagnosed at 3–6 months of age, often due to the kinky hair that is a striking feature of the disease. Late manifestations of the disease are blindness, subdural hematoma, and respiratory failure [2, 7, 8].

The skin may appear wrinkled and loose at birth from lysyl oxidase dysfunction. Hair depigmentation and skin pallor are due to tyrosinase deficiency, whereas pili torti and hair fragility are due to a reduced activity of sulfhydryl oxidase, responsible for the formation of disulfide bonds in the keratin of the hair [2].

All clinical forms of MD present pili torti in varying degrees [2, 3, 4, 5]. The hair is normal at birth and is replaced around 3 months of age by short, brittle, light-colored kinky hair characteristic of pili torti [9]. The areas of the scalp subject to friction are more affected, as was noted in our patient on the occipital region.

Light microscopy of the hair is an important bedside clinical tool for the diagnosis of various disorders affecting the hair and the adjacent scalp, including both congenital and acquired hair shaft anomalies [4, 5, 10]. For a long time, it has provided valuable diagnostic information in the setting of pediatric patients with immunological, hematological, or neurological impairment with hair involvement, such as in MD [4]. However, every time around 50 hairs have to be plucked or cut in order to decrease the risk of missing a hair with the characteristic dysplasia [10, 11]. Besides, it is common to find case reports of MD with hair images in which the twisting of the hair shafts is difficult to assess.

Rakowska et al. [5] and Rudnicka et al. [11] have demonstrated that characteristic light microscopy features of several genetic hair shaft dysplasias may be visualized by trichoscopy without the need of plucking hairs for diagnostic purposes. In our patient, the twisting of the hair shaft was more evident using trichoscopy than light microscopy examination, revealing pili torti in 50% of the hair shafts alternating with normal hair. This report highlights the usefulness of trichoscopy over hair light microscopy for the diagnosis of genodermatoses in which hair abnormalities have a distinctive characteristic, such as pili torti in MD, even before biochemical or genetic studies are performed to confirm the diagnosis.

Statement of Ethics

Written informed consent was obtained from the patient's parents for publication of their case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received.

Author Contributions

Carola Durán-McKinster made substantial contributions to the conception, drafting, and critically revising the work for important intellectual content. Ana Sylvia Aguilar-Sarmiento, Maria Adelaida Garcés-Abad, and Paulina Vázquez made substantial contributions to the acquisition and analysis of data for the article and drafting the work. Maria Teresa García-Romero and Marimar Sáez-de-Ocariz made substantial contributions to the design of the work and revised it critically for important intellectual content.