Dermatology Online Journal

Menkes kinky hair syndrome: A case report
Sangita Ghosh MBBS DDVL, Soumik Chaudhuri MBBS MD Medicine
Dermatology Online Journal 18 (11): 4

PGIMS, Rohtak, Haryana, India

---

Abstract

Menkes kinky hair syndrome, also known as trichopoliodystrophy, is a rare X-linked recessive, progressive neurodegenerative disorder characterized clinically by progressive psychomotor impairment, treatment-refractory seizures, and hair shaft abnormalities, most commonly pilli torti. The condition is related to a mutation in a copper transporting gene, located in the X-chromosome, resulting in deficiency of copper dependent enzymes. The diagnosis can be confirmed by a low plasma level of copper and ceruloplasmin. The prognosis of classical Menkes disease is poor. We report a case of Menkes kinky hair disease with characteristic clinical, laboratory, and radiological findings with significant macrocephaly (above 95th percentile for age). Reporting of this case is of significance because of its rarity and association with significant macrocephaly.

---

Introduction

Menkes disease (MD), also known as kinky hair disease or trichopoliodystrophy or steely hair disease, is an X-linked neurodegenerative disease of abnormal copper transport, resulting in copper maldistribution and relative deficiency in tissues like serum, brain, and liver [1, 2]. Menkes et al first described the disease in 1962 and ten years later Danks et al identified abnormal copper metabolism to be the etiology [3, 4]. The MD gene is located in the X chromosome in the 13.3 area, which encodes a copper transporting P-type ATPase (ATP 7A) [1]. The clinical features are related to deficiency of copper dependent enzymes and are characterized by progressive neurological disorders (evidenced by psychomotor deterioration and refractory epilepsy) and thin, brittle hair with a characteristic cherubic (angel-like) facial appearance [1, 5, 6]. The most characteristic finding is the sparse, thin, brittle and hypopigmented scalp hair. Examination under light microscope reveals hair shaft abnormalities, most commonly classic pili torti [7]. We hereby describe a case of classical Menkes disease with characteristic clinical and laboratory findings and macrocephaly.

Case report

A seven-month-old male infant was referred to our Dermatology outpatient department from the department of Pediatric medicine because of sparse, hypopigmented, abnormal scalp hair growth since birth. The patient was the second child of two asymptomatic non-consanguineous parents, born at 32 weeks of gestational age by normal vaginal delivery. The child had an abnormally large head at birth (details not available) and his birth weight was 1.7 kg (less than 3rd percentile). The neonatal period was uneventful. There is documented history of myoclonic jerks and gradual onset of hypotonia since three months of age. The mother reports delay in attaining developmental millestones such as recognition of mother, head control, social smile, or roll-over response. He has no feeding difficulties or any history suggestive of hypothermia. The child had two brief hospital admissions in the past two months because of recurrent chest infections. The parents have another 5-year-old son who is asymptomatic. Family history is unremarkable.

On examination the child had a characteristic cherubic face with depressed nasal bridge and bilateral large ears. Scalp hairs were sparse, brittle, stubby, hypopigmented with a steel wire like feel. The child also had a “cradle cap” on the scalp. Eyebrows and eyelashes were normal. There were no other abnormal cutaneous findings. He had remarkable macrocephaly with a head circumference of 50 cm, which is >95th percentile for age (normal head circumference for a seven month old child is 44 cm) with a considerable head lag. The child failed to make eye contact and there was absence of social smile. Deep tendon reflexes were brisk with significant hypotonia. Pupils were normal and reactive to light. Other systemic examinations were uneventful. Light microscopic examination of hair shaft of the patient showed pili-torti.

Figure 1	Figure 2
Figure 1. 1A) An infant with hypopigmented, sparse scalp hair and macrocephaly, depressed nasal bridge, large pinnae and a cherubic face. 1B) Same infant with a head lag on lifting by the arms. 1C) Demonstration of hypotonia in the same infant. Figure 2. 2A) Light microscopy of hair shaft under 10x magnification showing pilli torti. 2B) Pilli torti under 45X magnification by light microscopy.

With these findings, a provisional diagnosis of Menkes disease was made, which was confirmed by low serum concentration of serum copper, which was 9 µg\dl (ref: 70-150 µg\dl) and serum ceruloplasmin, which was 36 mg\l (ref: 187-320 mg\l). Routine blood investigations revealed no other abnormalities except macrocytic anemia with Hb of 8g\dl. Urine analysis was unremarkable. Chest x-ray and other joint x-rays were within normal limits. Computed tomography of brain showed hypodensity in the white matter of bilateral temporal area and mildly in left parietal lobe, with rest of the cerebral hemisphere having a normal attenuation pattern. There was no evidence of subdural hematoma or ventricular abnormalities accounting for the macrocephaly. Parents did not consent for magnetic resonance imaging of brain of the child.

Figure 3
Figure 3. Computed tomography of brain showing hypodense lesions in white matter of bilateral temporal and mildly in left parietal lobe.

Discussion

Menkes disease is a rare, inherited, metabolic disorder, with an estimated incidence of 1 in 114000 - 250000 live births [8]. It is characterized by psychomotor deterioration, refractory epilepsy, thin and brittle hypopigmented hair, skin pallor, and hypothermia. These clinical features are related to cuproenzyme deficiencies such as Lysyl oxidase (causing tortuous cerebral arteries), Cytochrome c oxidase (causing hypothermia), and Tyrosinase (resulting in hypopigmentation of hair and skin pallor) [5, 9]. There are a few variants of MD, such as a mild variant, neonatal variant, and occipital horn syndrome. Infants with classical MD are usually healthy until 2-3 months of age, when the disease starts to manifest with developmental delay, failure to thrive, intractable seizures and progressive hypotonia with a characteristic cherubic face [1, 5, 6].

Hair shaft abnormality is one of the striking features of this disease. Clinically, the scalp hairs appear sparse, coarse, short, and lightly pigmented. They are fragile and break easily, resulting in apparent alopecia. Hair shaft microscopy most commonly reveals pilli torti (180º twisted on axis). Other hair shaft abnormalities that are occasionally seen are trichorrhexis nodosa, trichoclasis, and monilethrix [7].

Refractory epilepsy is another important feature in MD. Myoclonus, characterized by brief, rapid, shock like jerky movements (focal or generalized) is the usual seizure type seen in MD. Rarely tonic spasm and multifocal seizures can also be seen. Lysyl oxidase deficiency causes formation of abnormal intracranial vessels, which fail to supply the brain adequately. Neuro-imaging discloses atrophy, ishchemic lesions in the deep gray matter or in cortical areas, and subdural hematomas [10].

History and clinical presentation, along with characteristic hair shaft microscopic findings, make the diagnosis easy. Low serum concentration of copper and ceruloplasmin would support the diagnosis further [6]. The final diagnosis can be confirmed by demonstrating impaired copper metabolism in cultured skin fibroblasts and lymphoblasts from the patient [9]. Pre-natal diagnosis of Menkes disease can be made by gene analysis and measuring concentration of copper in the culture of amniotic liquid cells and chorionic villi cells [11].

Management of patients with MD is supportive, with an emphasis on anti-convulsant treatment. Treatment of the mild variant of MD with copper histidine has been described in the literature. Copper histidine normalizes plasma copper and ceruloplasmin, which leads to a marked reduction of epileptic discharges, improves muscular tone, and increases motor activity [12]. The prognosis is poor with progressive deterioration and eventual death within the first three years of life [5].

The significance of this case report lies in its rarity and the association with macrocephaly since birth, without any evidence of ventricular dilatation or subdural effusion.

References

1. Menkes JH. Kinky hair disease. Pediatrics. 1972; 50:181-3. [PubMed]

2. Danks DM, Campbel PE, Walker-Smith J, Stevens BJ, Gillespie JM, Blomfield J, et al. Menkes Kinky hair syndrome. Lancet. 1972; 1:1100-2. [PubMed]

3. Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebral and cerebellar degeneration. Pediatr. 1962; 29:764-79. [PubMed]

4. Danks DM, Campbel PE, Stevens BJ, Mayne V, Cartwright E. Menkes kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatr. 1972; 50:188-201. [PubMed]

5. Menkes JH. Kinky hair disease: twenty five years later. Brain Dev. 1998; 10:77-9. [PubMed]

6. Menkes JH, Wilcox WR. Inherited metabolic disease of the nervous system. In: Menkes JH, Sarnet HB, Maria BL (eds). Child Neurology. 7th ed. Philadelphia: Lippincott Williams and Wilkins. 2006; Pp: 115-7.

7. Smith VB, Anderson G, Malone M, Sebire NJ. Light microscopic examination of scalp hair samples as an aid in the diagnosis of pediatric disorders: retrospective review of more than 300 cases from a single centre. J Clin Pathol. 2005; 58: 1294-8. [PubMed]

8. Tonnesen T, Kleijer WJ, Horn N. Incidence of Menkes disease. Human Genet. 1991; 86: 408-10. [PubMed]

9. Tumer Z, Horn N. Menkes disease: recent advances and new aspects. J Med Genet. 1997; 34:265-74. [PubMed]

10. Bahi-Buisson N, Kamniska A, Nabbout R, Barnerias C, Desquerre I,De Lonlay P, et al. Epilepsy in Menkes disease: Analysis of clinical stages. Epilepsia. 2006; 47:380-6. [PubMed]

11. Gu YU, Kodana H, Sato E, Mochizuki D, Yanagawa Y, Takayanagi M, et al. Prenatal diagnosis of Menkes disease by genetic analysis and copper measurement. Brain Dev. 2002; 24: 715-8. [PubMed]

12. Christodoulou J, Danks DM, Sarkar B, Baerlocher KE, Casey R, Horn N, et al. Early treatment of Menkes disease with parenteral copper-histidine: long-term follow up of four treated patients. Am J Med Genet. 1998; 76:154-164. [PubMed]

© 2012 Dermatology Online Journal