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Marden-Walker syndrome(MWKS)

MedGen UID:
163206
Concept ID:
C0796033
Disease or Syndrome
Synonyms: Connective tissue disorder Marden Walker type; MWKS
SNOMED CT: Marden Walker syndrome (449824004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PIEZO2 (18p11.22-11.21)
 
Monarch Initiative: MONDO:0009564
OMIM®: 248700
Orphanet: ORPHA2461

Definition

Marden-Walker syndrome (MWKS) is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis, and joint contractures. Other features may include Dandy-Walker malformation with hydrocephalus and vertebral abnormalities (summary by Schrander-Stumpel et al., 1993). There are 2 distal arthrogryposis syndromes with features overlapping those of Marden-Walker syndrome that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 3 (DA3, or Gordon syndrome; 114300) and distal arthrogryposis type 5 (DA5; 108145), which are distinguished by the presence of cleft palate and ocular abnormalities, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers ("spider fingers").
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Dextrocardia
MedGen UID:
4255
Concept ID:
C0011813
Congenital Abnormality
The heart is located in the right hand sided hemithorax. That is, there is a left-right reversal (or "mirror reflection") of the anatomical location of the heart in which the heart is locate on the right side instead of the left.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Zollinger-Ellison syndrome
MedGen UID:
53129
Concept ID:
C0043515
Disease or Syndrome
A condition in which there is increased production of gastrin by a gastrin-secreting tumor (usually located in the pancreas, duodenum, or abdominal lymph nodes) that stimulates the gastric mucosa to maximal activity, with consequent gastrointestinal mucosal ulceration.
Congenital hypertrophic pyloric stenosis
MedGen UID:
196010
Concept ID:
C0700639
Congenital Abnormality
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioral motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Inferior cerebellar vermis hypoplasia
MedGen UID:
343328
Concept ID:
C1855350
Congenital Abnormality
Underdevelopment of the inferior portion of the vermis of cerebellum.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Dandy-Walker syndrome
MedGen UID:
4150
Concept ID:
C0010964
Disease or Syndrome
Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985).
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Joint contracture of the hand
MedGen UID:
56382
Concept ID:
C0158113
Finding
Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Radioulnar synostosis
MedGen UID:
57861
Concept ID:
C0158761
Congenital Abnormality
An abnormal osseous union (fusion) between the radius and the ulna.
Congenital contracture
MedGen UID:
83066
Concept ID:
C0332878
Congenital Abnormality
One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Decreased muscle mass
MedGen UID:
373256
Concept ID:
C1837108
Finding
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Abnormal sternum morphology
MedGen UID:
349830
Concept ID:
C1860493
Anatomical Abnormality
An anomaly of the sternum, also known as the breastbone.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Fixed facial expression
MedGen UID:
344480
Concept ID:
C1855353
Finding
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMarden-Walker syndrome
Follow this link to review classifications for Marden-Walker syndrome in Orphanet.

Recent clinical studies

Etiology

Zapata-Aldana E, Al-Mobarak SB, Karp N, Campbell C
Am J Med Genet A 2019 Jun;179(6):1034-1041. Epub 2019 Apr 1 doi: 10.1002/ajmg.a.61143. PMID: 30938034
Verhagen JM, Schrander-Stumpel CT, Krapels IP, de Die-Smulders CE, van Lint FH, Willekes C, Weber JW, Gavilanes AW, Macville MV, Stegmann AP, Engelen JJ, Bakker J, Vos YJ, Frints SG
Eur J Med Genet 2011 Nov-Dec;54(6):e542-7. Epub 2011 Jul 30 doi: 10.1016/j.ejmg.2011.06.005. PMID: 21839187
Dentici ML, Mingarelli R, Dallapiccola B
Am J Med Genet A 2011 Mar;155A(3):459-65. Epub 2011 Feb 22 doi: 10.1002/ajmg.a.33642. PMID: 21567902
Theys T, Van Geet C, Didgar M
J Pediatr Surg 2011 Apr;46(4):e35-e37. doi: 10.1016/j.jpedsurg.2011.01.006. PMID: 21496524
Soekarman D, Volcke P, Legius E, Holvoet M, Fryns JP
Genet Couns 1996;7(1):31-9. PMID: 8652086

Diagnosis

Seidahmed MZ, Maddirevula S, Miqdad AM, Al Faifi A, Al Samadi A, Alkuraya FS
Am J Med Genet A 2021 Mar;185(3):945-948. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62052. PMID: 33369052
Niederhoffer KY, Fahiminiya S, Eydoux P, Mawson J, Nishimura G, Jerome-Majewska LA, Patel MS
Am J Med Genet A 2016 Sep;170(9):2310-21. Epub 2016 Jul 4 doi: 10.1002/ajmg.a.37831. PMID: 27375131
dos Santos AN, da Costa CS, de Campos AC, Rocha NA
Dev Neurorehabil 2014 Aug;17(4):278-83. Epub 2014 Mar 20 doi: 10.3109/17518423.2013.878406. PMID: 24649842
Ben-Neriah Z, Yagel S, Ariel I
Am J Med Genet 1995 Jul 3;57(3):417-9. doi: 10.1002/ajmg.1320570310. PMID: 7677143
Schrander-Stumpel C, de Die-Smulders C, de Krom M, Schyns-Fleuran S, Hamel B, Jaeken D, Fryns JP
Clin Genet 1993 Jun;43(6):303-8. doi: 10.1111/j.1399-0004.1993.tb03823.x. PMID: 8370150

Prognosis

Oliwa A, Hendson G, Longman C, Synnes A, Seath K, Barnicoat A, Hall JG, Patel MS
Am J Med Genet A 2023 Feb;191(2):546-553. Epub 2022 Nov 1 doi: 10.1002/ajmg.a.63019. PMID: 36317804
Niederhoffer KY, Fahiminiya S, Eydoux P, Mawson J, Nishimura G, Jerome-Majewska LA, Patel MS
Am J Med Genet A 2016 Sep;170(9):2310-21. Epub 2016 Jul 4 doi: 10.1002/ajmg.a.37831. PMID: 27375131
Winters KA, Jiang Z, Xu W, Li S, Ammous Z, Jayakar P, Wierenga KJ
Am J Med Genet A 2012 Nov;158A(11):2935-40. Epub 2012 Sep 14 doi: 10.1002/ajmg.a.35613. PMID: 22987394
Theys T, Van Geet C, Didgar M
J Pediatr Surg 2011 Apr;46(4):e35-e37. doi: 10.1016/j.jpedsurg.2011.01.006. PMID: 21496524
Soekarman D, Volcke P, Legius E, Holvoet M, Fryns JP
Genet Couns 1996;7(1):31-9. PMID: 8652086

Clinical prediction guides

Niederhoffer KY, Fahiminiya S, Eydoux P, Mawson J, Nishimura G, Jerome-Majewska LA, Patel MS
Am J Med Genet A 2016 Sep;170(9):2310-21. Epub 2016 Jul 4 doi: 10.1002/ajmg.a.37831. PMID: 27375131
dos Santos AN, da Costa CS, de Campos AC, Rocha NA
Dev Neurorehabil 2014 Aug;17(4):278-83. Epub 2014 Mar 20 doi: 10.3109/17518423.2013.878406. PMID: 24649842
Carrascosa-Romero MC, Suela J, Pardal-Fernández JM, Bermejo-Sánchez E, Vidal-Company A, MacDonald A, Tébar-Gil R, Martínez-Fernández ML, Martínez-Frías ML
Am J Med Genet A 2013 Sep;161A(9):2281-90. Epub 2013 Jul 25 doi: 10.1002/ajmg.a.35862. PMID: 23894067
Winters KA, Jiang Z, Xu W, Li S, Ammous Z, Jayakar P, Wierenga KJ
Am J Med Genet A 2012 Nov;158A(11):2935-40. Epub 2012 Sep 14 doi: 10.1002/ajmg.a.35613. PMID: 22987394
Arahori H, Tamura A, Wasada K, Shimoya K, Wada K, Murata Y, Ozono K
J Obstet Gynaecol Res 2007 Jun;33(3):248-53. doi: 10.1111/j.1447-0756.2007.00519.x. PMID: 17578350

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