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Marshall syndrome(MRSHS)

MedGen UID:
82694
Concept ID:
C0265235
Disease or Syndrome
Synonyms: Deafness, myopia, cataract, saddle nose-Marshall type; MRSHS
SNOMED CT: Marshall's syndrome (33410002); Marshall syndrome (33410002)
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): COL11A1 (1p21.1)
 
Monarch Initiative: MONDO:0007949
OMIM®: 154780
Orphanet: ORPHA560

Definition

Marshall syndrome (MRSHS) is characterized by midfacial hypoplasia, cleft palate, ocular anomalies including high myopia and cataracts, sensorineural hearing loss, short stature with spondyloepiphyseal dysplasia, and arthropathy. In contrast to Stickler syndrome type II, it has less severe eye findings but striking ocular hypertelorism, more pronounced maxillary hypoplasia, and ectodermal abnormalities (summary by Shanske et al., 1997 and Ala-Kokko and Shanske, 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia), which means they have trouble seeing things that are far away. In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.

In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.

A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.  https://medlineplus.gov/genetics/condition/stickler-syndrome

Clinical features

From HPO
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Osteoarthritis, knee
MedGen UID:
98371
Concept ID:
C0409959
Disease or Syndrome
Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)
Wide tufts of distal phalanges
MedGen UID:
322575
Concept ID:
C1835101
Finding
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Radial bowing
MedGen UID:
347136
Concept ID:
C1859399
Anatomical Abnormality
A bending or abnormal curvature of the radius.
Ulnar bowing
MedGen UID:
356099
Concept ID:
C1865847
Finding
Bending of the diaphysis (shaft) of the ulna.
Clinodactyly of the 4th finger
MedGen UID:
868093
Concept ID:
C4022484
Congenital Abnormality
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
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.
Calcification of falx cerebri
MedGen UID:
237237
Concept ID:
C1397139
Disease or Syndrome
The presence of calcium deposition in the falx cerebri.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Irregular femoral epiphysis
MedGen UID:
340592
Concept ID:
C1850658
Finding
Absent frontal sinuses
MedGen UID:
343405
Concept ID:
C1855669
Finding
Aplasia of frontal sinus.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Hypoplastic ilia
MedGen UID:
348814
Concept ID:
C1861218
Finding
Underdevelopment of the ilium.
Meningeal calcification
MedGen UID:
867790
Concept ID:
C4022181
Finding
Calcium deposition affecting the Meninges.
Small proximal tibial epiphyses
MedGen UID:
868570
Concept ID:
C4022969
Anatomical Abnormality
Reduced size of the proximal epiphysis of the tibia.
Small distal femoral epiphysis
MedGen UID:
868571
Concept ID:
C4022970
Finding
Reduced size of the Distal epiphysis of femur.
Irregular proximal tibial epiphyses
MedGen UID:
870596
Concept ID:
C4025045
Anatomical Abnormality
Anomaly of the contour of the proximal epiphysis of the tibia such that its normally smooth appearance is irregular.
Irregular distal femoral epiphysis
MedGen UID:
870601
Concept ID:
C4025050
Anatomical Abnormality
Anomaly of the contour of the Distal epiphysis of femur such that its normally smooth appearance is irregular.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Isolated Pierre-Robin syndrome
MedGen UID:
19310
Concept ID:
C0031900
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulaties during the neonatal period (summary by Tan et al., 2013).
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).
Macrodontia of permanent maxillary central incisor
MedGen UID:
371973
Concept ID:
C1835095
Finding
Increased size of the maxillary central secondary incisor tooth.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
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).
Thick upper lip vermilion
MedGen UID:
339521
Concept ID:
C1846423
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
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).
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Hypoplastic nasal bone
MedGen UID:
1814212
Concept ID:
C5676634
Congenital Abnormality
Length of the nasal bone below a predetermined cut-off as seen on antenatal ultrasound using standard imaging techniques.
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
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).
Lens luxation
MedGen UID:
6043
Concept ID:
C0023309
Injury or Poisoning
Complete dislocation of the lens of the eye.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Vitreoretinopathy
MedGen UID:
87480
Concept ID:
C0344290
Disease or Syndrome
Ocular abnormality characterized by premature degeneration of the vitreous and the retina that may be associated with increased risk of retinal detachment.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMarshall syndrome
Follow this link to review classifications for Marshall syndrome in Orphanet.

Professional guidelines

PubMed

Dusser P, Hentgen V, Neven B, Koné-Paut I
Joint Bone Spine 2016 Jul;83(4):406-11. Epub 2016 Apr 7 doi: 10.1016/j.jbspin.2015.08.017. PMID: 27068612

Recent clinical studies

Etiology

Higuchi Y, Hasegawa K, Yamashita M, Tanaka H, Tsukahara H
J Med Case Rep 2017 Aug 26;11(1):237. doi: 10.1186/s13256-017-1396-y. PMID: 28841907Free PMC Article
Dusser P, Hentgen V, Neven B, Koné-Paut I
Joint Bone Spine 2016 Jul;83(4):406-11. Epub 2016 Apr 7 doi: 10.1016/j.jbspin.2015.08.017. PMID: 27068612
Sardhara J, Behari S, Jaiswal AK, Srivastava A, Sahu RN, Mehrotra A, Phadke S, Singh U
Acta Neurochir (Wien) 2013 Jul;155(7):1157-67. Epub 2013 May 5 doi: 10.1007/s00701-013-1717-x. PMID: 23645321
Brubaker JW, Mohney BG, Pulido JS, Babovic-Vuksanovic D
Ophthalmic Genet 2008 Dec;29(4):184-5. doi: 10.1080/13816810802406339. PMID: 19005991
Szymko-Bennett YM, Mastroianni MA, Shotland LI, Davis J, Ondrey FG, Balog JZ, Rudy SF, McCullagh L, Levy HP, Liberfarb RM, Francomano CA, Griffith AJ
Arch Otolaryngol Head Neck Surg 2001 Sep;127(9):1061-8. doi: 10.1001/archotol.127.9.1061. PMID: 11556853

Diagnosis

Gardner NJ
JAAPA 2023 Oct 1;36(10):1-5. doi: 10.1097/01.JAA.0000977712.81696.b9. PMID: 37751263
Tomčíková D, Bušányová B, Krásnik V, Gerinec A
Cesk Slov Oftalmol 2018 Winter;74(3):108-111. doi: 10.31348/2018/1/5-3-2018. PMID: 30650974
Webb K, Hlela C, Jordaan HF, Suliman S, Scriba T, Lipsker D, Scott C
Pediatr Dermatol 2015 Jul-Aug;32(4):437-46. Epub 2015 Feb 26 doi: 10.1111/pde.12502. PMID: 25727235
Çalışkan E, Açıkgöz G, Yeniay Y, Özmen İ, Gamsızkan M, Akar A
Int J Dermatol 2015 Jun;54(6):e217-21. Epub 2014 Sep 10 doi: 10.1111/ijd.12471. PMID: 25208889
Priya J, Joshi S
Indian Pediatr 2005 Feb;42(2):177-8. PMID: 15767717

Therapy

Jagati A, Shrivastava S, Baghela B, Agarwal P, Saikia S
J Cutan Pathol 2020 Feb;47(2):146-149. Epub 2019 Aug 30 doi: 10.1111/cup.13567. PMID: 31437319
Dusser P, Hentgen V, Neven B, Koné-Paut I
Joint Bone Spine 2016 Jul;83(4):406-11. Epub 2016 Apr 7 doi: 10.1016/j.jbspin.2015.08.017. PMID: 27068612

Prognosis

Dusser P, Hentgen V, Neven B, Koné-Paut I
Joint Bone Spine 2016 Jul;83(4):406-11. Epub 2016 Apr 7 doi: 10.1016/j.jbspin.2015.08.017. PMID: 27068612

Clinical prediction guides

Bacciu A, Di Lella F, Iaccarino I, Pasanisi E, Fava G, Vincenti V, Falcioni M
Otol Neurotol 2018 Sep;39(8):e691-e698. doi: 10.1097/MAO.0000000000001896. PMID: 30020262
Dusser P, Hentgen V, Neven B, Koné-Paut I
Joint Bone Spine 2016 Jul;83(4):406-11. Epub 2016 Apr 7 doi: 10.1016/j.jbspin.2015.08.017. PMID: 27068612
Sardhara J, Behari S, Jaiswal AK, Srivastava A, Sahu RN, Mehrotra A, Phadke S, Singh U
Acta Neurochir (Wien) 2013 Jul;155(7):1157-67. Epub 2013 May 5 doi: 10.1007/s00701-013-1717-x. PMID: 23645321
Brubaker JW, Mohney BG, Pulido JS, Babovic-Vuksanovic D
Ophthalmic Genet 2008 Dec;29(4):184-5. doi: 10.1080/13816810802406339. PMID: 19005991
Szymko-Bennett YM, Mastroianni MA, Shotland LI, Davis J, Ondrey FG, Balog JZ, Rudy SF, McCullagh L, Levy HP, Liberfarb RM, Francomano CA, Griffith AJ
Arch Otolaryngol Head Neck Surg 2001 Sep;127(9):1061-8. doi: 10.1001/archotol.127.9.1061. PMID: 11556853

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