Marden-Walker syndrome - Rare Pediatrics News

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Disease Profile

Marden-Walker syndrome

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US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

Q87.0

Inheritance

Marden-Walker syndrome is thought to be inherited in an autosomal recessive manner.^[1]^[7] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

MWS; Connective tissue disorder Marden Walker type

Summary

Marden-Walker syndrome (MWS) is a genetic condition affecting the connective tissue. MWS is very rare and information about this condition is based on less than 50 people. Features may include distinctive facial features, a cleft or high-arched palate, a small or receding jaw (micrognathia), fixed bone joints (contractures or arthrogryposis), and growth delay. Other 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. The cause of MWS is unknown. A few individuals have been found to have a PIEZO2 gene that is not working correctly. It is likely inherited in an autosomal recessive pattern.^[1] This condition is diagnosed by a clinical exam and other medical tests. Treatment is based on managing the symptoms.^[2]^[3]^[4]

Symptoms

The following list includes the most common signs and symptoms in people with Marden-Walker syndrome (MWS). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.^[3]^[5]

Signs and symptoms include:

Mask-like face
Narrow eye opening (blepharophimosis)
Small mouth,
Small chin (micrognathia)
Cleft palate
Frozen joints (joint contractures)
Intellectual disability
Decreased muscle mass

Additional features may include arachnodactyly, chest deformities, curvature of the spine, and absent deep tendon reflexes. Some individuals have kidney, heart, or brain abnormalities.^[4]^[6]

Marden-Walker syndrome (MWS) is very rare and little information is known about how the disease changes over time. Most signs of MWS are present at birth or in early infancy. As children with this condition grow, they may develop failure to thrive and intellectual disability. The joint contractures may get better with time.^[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

The cause of Marden-Walker syndrome is unknown. Some individuals have been found to have a PIEZO2 gene that is not working correctly.^[1]^[3]

Diagnosis

Marden-Walker syndrome (MWS) is diagnosed based on a clinical history, exam, and additional medical tests, such as imaging and nerve conduction studies. In addition, several other conditions resemble Marden-Walker syndrome and may need to be excluded.^[6]

Treatment

Treatment for Marden-Walker syndrome (MWS) is based on managing the symptoms.^[2]^[3]

Specialists who may be involved in the care of someone with Marden-Walker syndrome include:

Medical geneticist
Neurologist
Orthopedist
Physical therapist
Occupational therapist

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Aplasia/Hypoplasia involving the skeletal musculature	Absent/small skeletal muscles Absent/underdeveloped skeletal muscles [ more ]	0001460
Arachnodactyly	Long slender fingers Spider fingers [ more ]	0001166
Arthrogryposis multiplex congenita		0002804
Bifid uvula		0000193
Blepharophimosis	Narrow opening between the eyelids	0000581
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Global developmental delay		0001263
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Mask-like facies	Expressionless face Lack of facial expression Mask-like facial appearance [ more ]	0000298
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Muscular dystrophy		0003560
Muscular hypotonia	Low or weak muscle tone	0001252
Narrow mouth	Small mouth	0000160
Posteriorly rotated ears	Ears rotated toward back of head	0000358
Ptosis	Drooping upper eyelid	0000508
Radioulnar synostosis	Fused forearm bones	0002974
Retrognathia	Receding chin Receding lower jaw Weak chin Weak jaw [ more ]	0000278
Severe short stature	Dwarfism Proportionate dwarfism Short stature, severe [ more ]	0003510
Short palpebral fissure	Short opening between the eyelids	0012745
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Specific learning disability		0001328
Submucous cleft hard palate		0000176
30%-79% of people have these symptoms
Attention deficit hyperactivity disorder	Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ]	0007018
Camptodactyly of finger	Permanent flexion of the finger	0100490
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Kyphosis	Hunched back Round back [ more ]	0002808
Pectus carinatum	Pigeon chest	0000768
Pectus excavatum	Funnel chest	0000767
Scoliosis		0002650
5%-29% of people have these symptoms
Abnormal form of the vertebral bodies		0003312
Abnormality of the cerebellar vermis		0002334
Absent septum pellucidum		0001331
Agenesis of corpus callosum		0001274
Cerebellar hypoplasia	Small cerebellum Underdeveloped cerebellum [ more ]	0001321
Epispadias		0000039
Hydrocephalus	Too much cerebrospinal fluid in the brain	0000238
Hydronephrosis		0000126
Hydroureter		0000072
Hypospadias		0000047
Metatarsus adductus	Front half of foot turns inward	0001840
Multicystic kidney dysplasia		0000003
Pyloric stenosis		0002021
Renal agenesis	Absent kidney Missing kidney [ more ]	0000104
Renal dysplasia		0000110
Situs inversus totalis	All organs on wrong side of body	0001696
Talipes		0001883
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Percent of people who have these symptoms is not available through HPO
Abnormal sternum morphology	Abnormality of the sternum Sternal anomalies [ more ]	0000766
Anteverted nares	Nasal tip, upturned Upturned nasal tip Upturned nose Upturned nostrils [ more ]	0000463

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes trisomy 13 and 18, Smith-Lemli-Opitz syndrome, Zellweger syndrome, spinal cord injury, amyoplasia congenita, infantile spinal muscular atrophy, Moebius syndrome, congenital hypomyelinating neuropathy, blepharophimosis-intellectual deficit syndromes, Van den Ende-Gupta syndrome, Freeman-Sheldon syndrome, Schwartz-Jampel syndrome (same clinical presentation but MWS lacks myotonia), infantile neuronal degeneration and focal infantile spinal muscular atrophy. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

Differential diagnosis includes trisomy 13 and 18, Smith-Lemli-Opitz syndrome, Zellweger syndrome, spinal cord injury, amyoplasia congenita, infantile spinal muscular atrophy, Moebius syndrome, congenital hypomyelinating neuropathy, blepharophimosis-intellectual deficit syndromes, Van den Ende-Gupta syndrome, Freeman-Sheldon syndrome, Schwartz-Jampel syndrome (same clinical presentation but MWS lacks myotonia), infantile neuronal degeneration and focal infantile spinal muscular atrophy.

Visit the Orphanet disease page for more information.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Marden-Walker syndrome. Click on the link to view a sample search on this topic.

References

McMillin, M et al. Mutations in PIEZO2 Cause Gordon Syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5. Am J Hum Genet. May 1, 2014; 94(5):734-44. https://www.ncbi.nlm.nih.gov/pubmed/24726473.
Marden Walker Syndrome. National Organization for Rare Disorders (NORD). 2004; https://rarediseases.org/rare-diseases/marden-walker-syndrome/. Accessed 8/3/2016.
Injeti G, Taksande A. Marden-Walker syndrome. Orphanet. Updated Dec 2019; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2461.
Theys T, Van Geet C, Didgar M. Novel findings in the Marden-Walker syndrome. J Pediatr Surg. 2011; 46(4):e35-e37. https://pubmed.ncbi.nlm.nih.gov/21496524.
Dumic M, Rojnic-Putarek N, Skrablin-Kucic S, Matic T, Ille J, Radica A. Marden-Walker syndrome--a case report. Lijec Vjesn. 2009; https://www.ncbi.nlm.nih.gov/pubmed/19769282. Accessed 5/27/2011.
Niederhoffer KY, Fahiminiya S, Eydoux P, Mawson J, Nishimura G, et al. Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders. Am J Med Genet A. 2016; 170(9):2310-2321. https://pubmed.ncbi.nlm.nih.gov/27375131.
Marden-Walker Syndrome. Online Mendelian Inheritance in Man (OMIM). Updated June 16, 2014; https://www.ncbi.nlm.nih.gov/omim/248700.

Rare Pediatrics News

Rare Pediatrics News

Rare Pediatrics News

Infancy

Q87.0

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Treatment

Related diseases

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.