Menkes Disease

What is Menkes Disease?

Menkes syndrome is a genetic disorder that affects how well the body absorbs copper.

It occurs in 1 in 100,000 live births, with the majority of individuals with the syndrome being born prematurely.

Due to the way in which it is inherited it occurs mainly in males.

Syndrome Synonyms:
Copper Transport Disease Kinky Hair Disease Kinky hair syndrome Menkes Syndrome Mk; Mnk MNK Steely Hair Disease

What gene changes cause Menkes Disease?

Mutations in the ATP7A gene cause the syndrome. As an X-linked recessive disorder it is inherited in the majority of cases and presents mainly in males. Some cases are caused by new mutations.

Syndromes inherited in an X-linked recessive pattern generally only affect males. Males only have one X chromosome, and so one copy of a gene mutation on it causes the syndrome. Females, with two X chromosomes, only one of which will be mutated, are not likely to be affected.

What are the main symptoms of Menkes Disease?

In infants the main and most severe symptoms are a failure to thrive and jaundice. Most individuals have unstable, low body temperatures.

Typical physical characteristics of the syndrome include very little, kinky hair as well as dry skin. Low muscle tone is another common symptom.

Health conditions associated with the syndrome include the deterioration of the nervous system, severe growth delay, brain and cognitive abnormalities as well as blood clots and osteoporosis.

Possible clinical traits/features:
Osteomyelitis, Abnormality of the face, Osteoporosis, Seizure, Venous insufficiency, Spontaneous hematomas, Sparse hair, Reduced bone mineral density, Tarsal synostosis, Wormian bones, Recurrent fractures, X-linked recessive inheritance, Umbilical hernia, Death in childhood, Abnormal hair quantity, Woolly hair, Sepsis, Microcephaly, Abnormal palate morphology, Dilatation, Atypical scarring of skin, Bladder diverticulum, Behavioral abnormality, Brachycephaly, Abnormal carotid artery morphology, Abnormality of the liver, Chondrocalcinosis, Chorea, Arterial stenosis, Aplasia/Hypoplasia of the abdominal wall musculature, Pectus excavatum, Metaphyseal widening, Metaphyseal spurs, Micrognathia, Mask-like facies, Intrauterine growth retardation, Intellectual disability, Intracranial hemorrhage, Muscle weakness, Muscular hypotonia, Narrow chest, Nausea and vomiting, Joint hypermobility, Joint laxity, Bowing of the long bones, Developmental regression, Thickened skin, Cutis laxa, Feeding difficulties in infancy, Exost

How does someone get tested for Menkes Disease?

The initial testing for Menkes syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow. 

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.   

Medical information on Menkes syndrome

This X-linked recessive condition is caused by a defect of copper transport and metabolism. Onset is in infancy with lethargy, abnormal temperature regulation, abnormal tone and seizures. Frequently there is prematurity. The face is said to be characteristic with pallor, full cheeks, tangled eyebrows and a pronounced cupid's bow to the upper lip. The hair may be normal at birth but becomes depigmented, thin and brittle. Microscopic analysis reveals pili torti. An alternative description for the hair abnormality is 'steely' hair. Neurological deterioration is progressive and death occurs before the age of 3. Aynaci et al., (1997) reported a case with cerebellar vermian hypoplasia and deafness. An MRI will show cortical and cerebellar atrophy with secondary subdural collections, and bizarre vascular tortuosity (Leventer et al., 1997). Pathological examination of the brain reveals neuronal degeneration, gliosis, optic degeneration and tortuous arteries with an abnormal intima and occlusion. A case with a skull fracture at birth was reported by Ubhi et al., (2000). A combination of massive subdural haematomas and metaphyseal spurs can initially suggest shaken baby syndrome (Nassgne et al., 2002). An occipital horn has been described in a case with onset at 8 months and a mutation in exon 3 (Gerard-Blanluet et al., (2004). Panlobular emphysemaand pulmonary hypertension, were the presenting features in the case described by Grange et al., (2005).
There is intracellular accumulation of copper in cultured cells, due to impaired outflow. This is the basis of diagnostic and prenatal tests. Prenatal diagnosis can be carried out on chorionic villi, but the results are very susceptible to exogenous copper contamination. Carrier detection can also be attempted, but is subject to the usual problems with non-random X inactivation. Tumer et al., (1994) reported prenatal diagnosis by direct DNA analysis. Kaler and Tumer (1998) review prenatal diagnosis in Menkes syndrome. Monozygotic females were reported by Burgemeister et al., (2015), one being healthy the other dying from full-blown Menkes Disease.
The gene maps to Xq13 close to PGK. Females with an apparently balanced X;autosome translocation have been reported (Kapur et al., 1987; Sugio et al., 1998) Chelly et al., (1993), Vulpe et al., (1993) and Mercer et al., (1993) reported the isolation of a candidate gene. There was homology with bacterial heavy metal binding protein genes and was most similar to a copper-transporting ATPase. Tumer and Horn (1997) provide a good review of the clinical and molecular aspects.
Therapy with subcutaneous administration of copper-histidine has been attempted. Sarkar et al., (1993) review the long-term results in seven patients, two of whom were thought to have done well neurologically as a result of the treatment. If delivery is induced at 35 weeks and treatment commenced then, neurological features may be much milder, but the patients develop features of occipital horn syndrome. Similar results were obtained by Christodoulou et al., (1998) in four patients. Tumer et al (1996) show that two treated patients with this phenotype originally reported by Sarkar et al., (1993) have potentially lethal mutations in the Menkes gene. Kaler (1996) suggests that not every infant with classical Menkes Disease will have the same level of benefit from early copper-histidine treatment.
Occasional patients have been reported with a milder form of the condition, presenting with ataxia (Danks et al., 1988; Procopis et al., 1981). Proud et al., (1996) stressed that some cases have clinical overlap with occipital horn syndrome and indeed mutations in the Menkes gene have been described in the latter condition.
The condition is expertly reviewed by Tumer and Moller (2010).

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

Get Faster and More Accurate Genetic Diagnosis!

More than 250,000 patients successfully analyzed!
Don't wait years for a diagnosis. Act now and save valuable time.

Start Here!

"Our road to a rare disease diagnosis was a 5-year journey that I can only describe as trying to take a road trip with no map. We didn’t know our starting point. We didn’t know our destination. Now we have hope."

Image

Paula and Bobby
Parents of Lillie

What is FDNA Telehealth?

FDNA Telehealth is a leading digital health company that provides faster access to accurate genetic analysis.

With a hospital technology recommended by leading geneticists, our unique platform connects patients with genetic experts to answer their most pressing questions and clarify any concerns they may have about their symptoms.

Benefits of FDNA Telehealth

FDNA icon

Credibility

Our platform is currently used by over 70% of geneticists and has been used to diagnose over 250,000 patients worldwide.

FDNA icon

Accessibility

FDNA Telehealth provides facial analysis and screening in minutes, followed by fast access to genetic counselors and geneticists.

FDNA icon

Ease of Use

Our seamless process begins with an initial online diagnosis by a genetic counselor and follows by consultations with geneticists and genetic testing.

FDNA icon

Accuracy & Precision

Advanced artificial intelligence (AI) capabilities and technology with a 90% accuracy rate for a more accurate genetic analysis.

FDNA icon

Value for
Money

Faster access to genetic counselors, geneticists, genetic testing, and a diagnosis. As fast as within 24 hours if required. Save time and money.

FDNA icon

Privacy & Security

We guarantee the utmost protection of all images and patient information. Your data is always safe, secure, and encrypted.

FDNA Telehealth can bring you closer to a diagnosis.
Schedule an online genetic counseling meeting within 72 hours!