Menke’s Kinky Hair Syndrome - A Spectrum of Clinico-Radiological findings

Case Report

Menke’s kinky hair syndrome e A spectrumof clinico-radiological findings

Alka Agrawal a, P.S. Tripathi b, Abhishree Geda c,*, Neha Nischal c

aAssociate Professor, Department of Radiodiagnosis, MGMMC & MY Hospital, Indore, M.P. 452001, IndiabAssisstant Professor, Department of Radiodiagnosis, MGMMC & MY Hospital, Indore, M.P. 452001, IndiacResident, Department of Radiodiagnosis, MGMMC & MY Hospital, Indore, M.P. 452001, India

a r t i c l e i n f o

Article history:

Received 23 October 2012

Accepted 18 February 2013

Available online 26 February 2013

Keywords:

Menkes disease

Copper metabolism

Pili torti

Tortuous intracranial vessels

Cerebral atrophy

a b s t r a c t

Menkes kinky hair syndrome is a fatal rare inherited neurodegenerative disease due to

deranged copper metabolism. The manifestations begin after 2e3 months of life with

developmental delay, intractable convulsions, typical facies and pili torti. Specific imaging

findings which strongly point towards the diagnosis include symmetrical bony spurs

around the knee joints, bladder diverticulas & brain atrophy with corkscrew tortuosity of

intra & extracranial vessels. Low serum copper and ceruloplasmin are confirmatory for the

disease. Here we present an interesting case with all classical findings of Menkes disease.

Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Case report

A 7-month-old male infant presented with progressively

increasing partial seizures with secondary generalisation

since one month. The history suggested a regression of pre-

viously achieved milestones such as smiling, recognition of

faces, cooing & playing with objects. The child had never

achieved head holding. The child was born to non-consan-

guineous parents and had an institutional normal vaginal

delivery at term with history of delayed cry.

There was a positive family history of successive

births of two male children with similar appearances &

complaints to the mother’s sister. Both these children sur-

vived for 3e4 months of age & neither of them was investi-

gated.

On examination, patient had lack of visual contact and

head holding with generalized hypotonia and lethargy. There

was microcephaly with parietal bossing. There were charac-

teristic hypopigmented, short, sparse, brittle, kinky, steely

hairs (Fig. 1). Skin was typically hypopigmented and doughy

with presence of cutis laxa.

The most significant abnormality found on the laboratory

workup was decreased copper and serum ceruloplasmin

levels measuring 9.4 mg/dl (N: 20e70 mg/dl) and 16.2 mg/dl (N:

20e60 mg/dl) respectively. The standard blood analyses

revealed anaemia with Hb levels 9.3 g/dl (N: 11e14 g/dl) &

hypocalcemia with S. Ca 7.84 mg/dl (N: 8.4e10.4 mg/dl).

Characteristic radiological abnormalities were found in the

infant. Skeletal X-rays revealed mild diffuse osteoporosis,

widened anterior end of ribs, metaphyseal flaring with

* Corresponding author.E-mail addresses: abhi308.neha@gmail.com, neha.nischal@gmail.com (A. Geda).

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symmetrical bony spurs in distal femoral & proximal tibial

bones & wormian bones in the skull (Fig. 2).

On ultrasound, a small diverticulum was seen along the

right lateral wall of urinary bladder.

On MRI, there was predominantly involvement of

subcortical white matter in the bilateral temporo-parietal &

frontal regions showing symmetric T1 hypointense & T2

hyperintense areas with mild prominence of CSF spaces

suggesting cerebral and cerebellar atrophy. Few patchy areas

of restricted diffusion were also seen in these and in the

ganglio-capsular regions. Striking tortuosities of the intra-

cranial as well as extracranial arteries were seen on MR

Fig. 1 e (a) The child with typical cherubic facies, cupid bow upper lip and hypopigmented skin. Sparse, coarse, lustreless,

kinky and steely hairs. (b) Light microscopy of hair reveals fractures in shaft & pili torti.

Fig. 2 e (a) X-ray knee joint showing bilateral distal femoral and proximal tibial spurs with metaphyseal widening. (b) 3DCT

Reconstruction demonstrating wormian bones along the lambdoid sutures.

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angiography. No subdural hygromas/haematomas were seen

(Fig. 3).

Based on the above clinico-radiological & laboratory

findings, the infant was diagnosed with Menke’s kinky hair

syndrome, also known as trichopoliodystrophy. Currently he

is on anticonvulsants but is showing no remarkable

improvement.

2. Discussion

Menke’s kinky hair disease or trichopoliodystrophy is a fatal

rare multisystem disorder with an incidence of about 1 in

1,00,000e2,50,000 births.1 It has X-linked inheritance resulting

in defective copper metabolism.

The usual presentation is after 2e3 months with psycho-

motor retardation, intractable seizures, hypotonia. There is

microcephaly, pudgy cheeks, cupid bow upper lip and cutis

laxa. However, themost striking feature of this rare disorder is

the presence of sparse kinky steely hair. The hairs typically

are hypopigmented, lustreless and break off easily. Micro-

scopic examination (Fig. 2) reveals most often pili torti2 (hair

twisted along its long axis), monilethrix (varying diameter of

hair shafts) and trichorrhexis nodosa (fractures of the hair shaft

at regular intervals).

2.1. Etio-pathogenesis3e5

2.2. Imaging findings

The common radiological features are progressive osteopo-

rosis, presence of wormian bones, flaring of anterior ends of

ribs & metaphyseal flaring around the knee joint with sym-

metrical spurs, scalloping of posterior surface of vertebral

bodies. Multiple large diverticulas of the urinary bladder may

be observed which predispose to recurrent UTI.

The MR findings1 suggestive of this disease are unique.

There are T1 hypointensities and T2 hyperintensities in the

cortical and subcortical white matter with corresponding

Mutation at gene locus Xq13.3 (ATP 7A gene)4

Defect in copper transporting protein (esp cerulopasmin)

Deficiency of key copper dependent enzymes

lysyl oxidase(collagen)

cytochrome c oxidase(cellular respiration)

dopamine -hydroxylase tyrosinase superoxide dismutase(neurotransmitter) (pigmentation) (antioxidant)

Hypothermia5 psychomotor retardation Hypopigmentation Recurrent infectionsTortuous intracranial arteries& decreased blood supply

Convulsions

Fig. 3 e T2WI (a) MRI images showing diffuse symmetric cerebral atrophy predominantly involving bilateral temporo-

parietal regions. MR angiography (b) showing the tortuosity of intracranial as well as extracranial arteries.

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hypointensities on FLAIR image, widening of CSF spaces and

prominence of cerebellar folia suggestive of severe neuronal

loss. Vascular compromise leads to demyelination of the

whitematter tracts. Theremay be areas of restricted diffusion

secondary to diffuse white matter ischaemia. Bilateral large

subdural hygromas suggests hemorrhages of different ages.

MR angiography reveals elongated and tortuous intra as

well as extracranial vessels (corkscrew pattern) which are

characteristic of the disease. MR spectroscopy shows elevated

lactate and reduced N-acetylaspartate (NAA)ecreatine (Cr)

ratio. The normalisation of MRS features suggests favourable

response to copper histidine treatment.

2.3. Laboratory findings

Low serum copper and ceruloplasmin levels5 are diagnostic

for the disease. Other supportive lab findings include hyper-

calciuria, albuminuria, aminoaciduria and increased excre-

tion of b2 microglobulin. Urinary homovanillic acid/

vanillylmandelic acid ratio �4 strongly suggests the disease

and thus could be used for screening.

2.4. Differential diagnosis

Presence of metaphyseal widening makes rickets an impor-

tant differential for this disease. Another common differential

for presence of subdural haematomas of different ages is

battered baby syndrome. However, the neurodevelopmental

history, typical hair and biochemical markers as described are

specific for Menkes syndrome.

3. Conclusion

The diagnosis in our case was made based on clinico-

radiologic and laboratory findings. Treatment of the disease

is conservative with anticonvulsants. Copper supplements

like intravenous copper or copper histidine have been tried.

Copper histidine was not given in our case due to lack of

availability.

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

1. Datta Asok K, Ghosh Taraknath, Nayak Kaustav,Ghosh Mrinalkanti. Menkes kinky hair disease: a case report.Cases J. 2008;1:158. http://dx.doi.org/10.1186/1757-1626-1-158.

2. Gandhi Rozil, Kakkar Ritu, Rajan Sajeev, Bhangale Rashmi,Desai Shrinivas. Menkes kinky hair syndrome: a rareneurodegenerative disease. Case Rep Radiol. 2012;2012:684309.

3. Kamolsilp MD Mahattana. Menkes syndrome: a case report.J Med Assoc Thai. 2005;88(suppl 3):S290eS294.

4. Tumer Zeynep, Møller Lisbeth B. Menkes disease. Eur J HumGenet. 2010 May;18(5):511e518.

5. Barzegar Mohammad, Fayyazie Afshin, Gasemie Bobollah,Shoja Mohammad Ali Mohajel. Menkes disease: report of twocases. Iran J Pediatr. 2007;17(3):388e392.

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