What are the other Names for this Condition? (Also known as/Synonyms)

• Connective Tissue Disorder, Marden Walker type
• MWS (Marden-Walker Syndrome)

What is Marden-Walker Syndrome? (Definition/Background Information)

• Marden-Walker Syndrome (MWS) is a connective tissue disorder characterized by distinctive facial features, a cleft or high-arched palate, a small or receding jaw (micrognathia), fixed bone joints (contractures or arthrogryposis), and growth delay
• Symptoms may include a mask-like face with a narrowing of the eye opening (blepharophimosis), low-set ears, failure to thrive and a generalized slowing down of physical reactions, movements, and speech
• While the underlying cause of Marden-Walker Syndrome has not been clearly established, it is believed to be a developmental disorder of the central nervous system which is inherited in an autosomal recessive manner
• Mutations in the PIEZO2 gene have been identified in a few individuals with Marden-Walker Syndrome
• Although there is no specific treatment or cure for Marden-Walker Syndrome, there are ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person

(Source: Marden-Walker Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Marden-Walker Syndrome? (Age and Sex Distribution)

• Marden-Walker Syndrome is a rare congenital disorder, with about 30-50 cases reported worldwide in the medical literature
• The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Marden-Walker Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Marden-Walker Syndrome can be an inherited condition
• Being a child of consanguineous parents may increase the risk of MWS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Marden-Walker Syndrome? (Etiology)

The exact cause of Marden-Walker Syndrome is not clearly known.

• It has been suggested that the condition may develop as a result of abnormalities in the developmental of the central nervous system
• Mutation(s) in the PIEZO2 gene have ben reported in some affected individuals
• The mode of inheritance appears to be autosomal recessive

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Marden-Walker Syndrome?

The Marden-Walker Syndrome may vary in type and severity among affected individuals, and include:

• Abnormality of the sternum
• Anteverted nares
• Camptodactyly 
• Cleft palate 
• Congenital contracture
• Cryptorchidism
• Dandy-Walker malformation 
• Decreased muscle mass
• Dextrocardia 
• Epicanthus
• Fixed facial expression
• Generalized hypotonia
• High, narrow palate
• Hypertelorism
• Hypoplasia of the brainstem
• Inferior vermis hypoplasia
• Inguinal hernia
• Joint contracture of the hand 
• Long philtrum 
• Micropenis
• Microphthalmia
• Postnatal growth retardation
• Primitive reflex 
• Pulmonary hypoplasia 
• Renal hypoplasia
• Seizures
• Short neck
• Strabismus
• Talipes equinovarus
• Wide anterior fontanel 
• Zollinger-Ellison syndrome

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Aplasia/hypoplasia involving the skeletal musculature
• Arachnodactyly
• Arthrogryposis multiplex congenita 
• Bifid uvula 
• Blepharophimosis
• Failure to thrive
• Feeding difficulties
• Global developmental delay 
• Intellectual disability
• Joint stiffness
• Low-set ears
• Mask-like facies
• Microcephaly
• Micrognathia 
• Muscular dystrophy 
• Muscular hypotonia 
• Narrow mouth
• Posteriorly rotated ears 
• Ptosis
• Radioulnar synostosis
• Retrognathia
• Severe short stature
• Short palpebral fissure
• Skeletal muscle atrophy
• Specific learning disability 
• Submucous cleft hard palate

Frequently present symptoms in 30-79% of the cases:

• Attention-deficit hyperactivity disorder (ADHD)
• Camptodactyly of finger 
• Intrauterine growth retardation
• Kyphosis
• Pectus carinatum
• Pectus excavatum 
• Scoliosis

Occasionally present symptoms in 5-29% of the cases:

• Abnormal form of the vertebral bodies 
• Abnormality of the cerebellar vermis 
• Absent septum pellucidum 
• Agenesis of corpus callosum 
• Cerebellar hypoplasia
• Epispadias 
• Hydrocephalus 
• Hydronephrosis 
• Hydroureter 
• Hypospadias 
• Metatarsus adductus 
• Multicystic kidney dysplasia 
• Pyloric stenosis 
• Renal agenesis 
• Renal dysplasia 
• Situs inversus totalis 
• Talipes 
• Ventricular septal defect

(Source: Marden-Walker Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Marden-Walker Syndrome Diagnosed?

Marden-Walker Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Marden-Walker Syndrome?

The complications of Marden-Walker Syndrome may include:

• Failure to thrive in the neonatal period
• Extreme difficulty in movement due to skeletal deformities
• Structural and functional abnormalities in organs of the chest cavity, if scoliosis is present
• Severe intellectual deficiency
• Behavioral problems such as aggression and hyperactivity
• Chronic kidney failure
• High risk of lung infections
• Heart attack

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Marden-Walker Syndrome Treated?

Presently, there is no cure for Marden-Walker Syndrome.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• A concerted effort by a group of medical professionals from different disciplines may be necessary for planning and administering the treatment

How can Marden-Walker Syndrome be Prevented?

Currently, Marden-Walker Syndrome may not be preventable, since it may be a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Marden-Walker Syndrome? (Outcomes/Resolutions)

• The prognosis of Marden-Walker Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• However, due to severe intellectual deficiency, incapacitating skeletal deformities, gastrointestinal abnormalities and risk of developing lung infections, the lifespan is generally affected
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Marden-Walker Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/