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Myhre syndrome(MYHRS)

MedGen UID:
167103
Concept ID:
C0796081
Disease or Syndrome
Synonyms: Growth mental deficiency syndrome of Myhre; LAPS SYNDROME; LARYNGOTRACHEAL STENOSIS, ARTHROPATHY, PROGNATHISM, AND SHORT STATURE; Laryngotracheal stenosis, progressive, with short stature and arthropathy; MYHRS
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Facial dysmorphism, intellectual deficit, short stature and hearing loss (699316006); Laryngotracheal stenosis, arthropathy, prognathism and short stature (699316006); Myhre syndrome (699316006)
 
Gene (location): SMAD4 (18q21.2)
OMIM®: 139210
Orphanet: ORPHA2588

Definition

Myhre syndrome is a rare disorder characterized by mental retardation, dysmorphic facial features, including microcephaly, midface hypoplasia, prognathism, and blepharophimosis, as well as typical skeletal anomalies, including short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur. All reported cases have been sporadic (summary by Bachmann-Gagescu et al., 2011). [from OMIM]

Additional description

From GHR
Myhre syndrome is a condition with features affecting many systems and functions of the body. People with Myhre syndrome usually have delayed development of language and motor skills such as crawling and walking. Most have intellectual disability that ranges from mild to moderate. Some have behavioral issues such as features of autism or related developmental disorders affecting communication and social interaction. People with Myhre syndrome often have hearing loss, which can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss). Growth is reduced in people with this disorder, beginning before birth and continuing through adolescence. Affected individuals have a low birth weight and are generally shorter than about 97 percent of their peers throughout life. People with Myhre syndrome typically have stiffness of the skin and are usually described as having a muscular appearance. Skeletal abnormalities associated with this disorder include thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, underdevelopment of the winglike structures of the pelvis (hypoplastic iliac wings), and unusually short fingers and toes (brachydactyly). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility. Typical facial features in people with Myhre syndrome include narrow openings of the eyelids (short palpebral fissures), a shortened distance between the nose and upper lip (a short philtrum), a sunken appearance of the middle of the face (midface hypoplasia), a small mouth with a thin upper lip, and a protruding jaw (prognathism). Some affected individuals also have an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Other features that occur in some people with this disorder include constriction of the throat (laryngotracheal stenosis), high blood pressure (hypertension), heart or eye abnormalities, and in males, undescended testes (cryptorchidism). A disorder sometimes called laryngotracheal stenosis, arthropathy, prognathism, and short stature (LAPS) syndrome is now generally considered to be the same condition as Myhre syndrome because it has similar symptoms and the same genetic cause.  http://ghr.nlm.nih.gov/condition/myhre-syndrome

Clinical features

Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Intrauterine growth retardation
MedGen UID:
342890
Concept ID:
C1853481
Finding
Obesity
MedGen UID:
368429
Concept ID:
C1963185
Finding
Cryptorchidism
MedGen UID:
504309
Concept ID:
CN000029
Finding
Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Displacement of the external urethral meatus
MedGen UID:
451918
Concept ID:
CN117519
Finding
A displacement of the external urethral orifice from its normal position (in males normally placed at the tip of glans penis, in females normally placed about 2.5 cm behind the glans clitoridis and immediately in front of that of the vagina).
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Prominent nasal bridge
MedGen UID:
324887
Concept ID:
C1837827
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Finding
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Malar flattening
MedGen UID:
347814
Concept ID:
C1859168
Finding
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Narrow mouth
MedGen UID:
504373
Concept ID:
CN000156
Finding
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Cleft palate
MedGen UID:
504379
Concept ID:
CN000170
Finding
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).
Oral cleft
MedGen UID:
504390
Concept ID:
CN000196
Finding
The presence of a cleft in the oral cavity, the two main types of which are cleft lip and cleft palate. In cleft lip, there is the congenital failure of the maxillary and median nasal processes to fuse, forming a groove or fissure in the lip. In cleft palate, there is a congenital failure of the palate to fuse properly, forming a grooved depression or fissure in the roof of the mouth. Clefts of the lip and palate can occur individually or together. It is preferable to code each defect separately.
Thin upper lip vermilion
MedGen UID:
507078
Concept ID:
CN000212
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Thin vermilion border
MedGen UID:
504403
Concept ID:
CN000225
Finding
Reduced width of the \
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Hypoplasia of the maxilla
MedGen UID:
446348
Concept ID:
CN000307
Finding
Underdevelopment of the Maxilla.
Deeply set eye
MedGen UID:
504464
Concept ID:
CN000458
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Microphthalmos
MedGen UID:
504501
Concept ID:
CN000533
Finding
A developmental anomaly characterized by abnormal smallness of one or both eyes.
Thick eyebrow
MedGen UID:
500889
Concept ID:
CN000539
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Blepharophimosis
MedGen UID:
504508
Concept ID:
CN000545
Finding
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Non-midline cleft lip
MedGen UID:
451693
Concept ID:
CN117231
Finding
Clefting of the upper lip affecting the lateral portions of the upper lip rather than the midline/median region.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
Strabismus is the intermittent or constant misalignment of an eye so that its line of vision is not pointed at the same object as the other eye. Strabismus is caused by an imbalance in the extraocular muscles which control the positioning of the eyes. Strabismus is normal in newborns but should resolve by the time the baby is 6 months old. In older children with strabismus, the brain may learn to ignore the input from one eye, and this may lead to amblyopia, a potentially permanent decrease in vision in that eye if not corrected.
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Deeply set eye
MedGen UID:
504464
Concept ID:
CN000458
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
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).
Hypermetropia
MedGen UID:
504484
Concept ID:
CN000506
Finding
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Microphthalmos
MedGen UID:
504501
Concept ID:
CN000533
Finding
A developmental anomaly characterized by abnormal smallness of one or both eyes.
Microtia
MedGen UID:
351220
Concept ID:
C1864797
Finding
Hearing impairment
MedGen UID:
446352
Concept ID:
CN000341
Finding
A decreased magnitude of the sensory perception of sound.
Low-set ears
MedGen UID:
504425
Concept ID:
CN000345
Finding
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.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Cognitive impairment
MedGen UID:
383844
Concept ID:
C1856145
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Behavioral abnormality
MedGen UID:
425007
Concept ID:
CN000665
Finding
An abnormality of mental functioning including various affective, behavioural, cognitive and perceptual abnormalities.
Autism
MedGen UID:
504569
Concept ID:
CN000674
Finding
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV).
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
Development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of PUBERTY in the population. This early maturation of the hypothalamic-pituitary-gonadal axis results in sexual precocity, elevated serum levels of GONADOTROPINS and GONADAL STEROID HORMONES such as ESTRADIOL and TESTOSTERONE.
Short finger
MedGen UID:
68683
Concept ID:
C0239594
Finding
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Microcephaly
MedGen UID:
337454
Concept ID:
C1845868
Finding
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Thickened calvaria
MedGen UID:
347516
Concept ID:
C1857647
Finding
Malar flattening
MedGen UID:
347814
Concept ID:
C1859168
Finding
Hypoplastic iliac wing
MedGen UID:
350044
Concept ID:
C1861530
Finding
2-3 toe syndactyly
MedGen UID:
400146
Concept ID:
C1862857
Finding
Platyspondyly
MedGen UID:
355353
Concept ID:
C1865023
Finding
Cone-shaped epiphysis
MedGen UID:
351282
Concept ID:
C1865037
Finding
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Radial deviation of finger
MedGen UID:
473540
Concept ID:
C2178410
Finding
Mandibular prognathia
MedGen UID:
427817
Concept ID:
CN000285
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Hypoplasia of the maxilla
MedGen UID:
446348
Concept ID:
CN000307
Finding
Underdevelopment of the Maxilla.
Abnormality of the ribs
MedGen UID:
427835
Concept ID:
CN000726
Finding
An anomaly of the rib.
Abnormality of the metaphyses
MedGen UID:
428237
Concept ID:
CN000883
Finding
An abnormality of one or more metaphysis, i.e., of the somewhat wider portion of a long bone that is adjacent to the epiphyseal growth plate and grows during childhood.
Brachydactyly syndrome
MedGen UID:
500899
Concept ID:
CN001088
Finding
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
Limitation of joint mobility
MedGen UID:
446405
Concept ID:
CN001260
Finding
A reduction in the freedom of movement of one or more joints.
Short toe
MedGen UID:
500911
Concept ID:
CN001658
Finding
A toe that appears disproportionately short compared to the foot.
Overlapping toe
MedGen UID:
504973
Concept ID:
CN001669
Finding
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest.
Abnormality of pelvic girdle bone morphology
MedGen UID:
428305
Concept ID:
CN002405
Finding
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Vertebral fusion
MedGen UID:
505419
Concept ID:
CN002669
Finding
A developmental defect leading to the union of two adjacent vertebrae.
Short long bone
MedGen UID:
832972
Concept ID:
CN002735
Finding
One or more abnormally short long bone.
Enlarged vertebral pedicles
MedGen UID:
505661
Concept ID:
CN004099
Finding
Increased size of the vertebral pedicle.
Camptodactyly
MedGen UID:
507335
Concept ID:
CN180568
Finding
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.
Clinodactyly
MedGen UID:
807884
Concept ID:
CN220788
Finding
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Hernia of the abdominal wall
MedGen UID:
428061
Concept ID:
CN003802
Finding
The presence of a hernia in the abdominal wall.
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Stiff skin
MedGen UID:
478445
Concept ID:
C3276815
Finding
Thick eyebrow
MedGen UID:
500889
Concept ID:
CN000539
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Thickened skin
MedGen UID:
504710
Concept ID:
CN001007
Finding
Laminar thickening of skin.
Sparse hair
MedGen UID:
501034
Concept ID:
CN007096
Finding
Reduced density of hairs.
Abnormality of the voice
MedGen UID:
425062
Concept ID:
CN001464
Finding
Any abnormality of the voice.
Hypertension
MedGen UID:
635666
Concept ID:
C0497247
Finding
A finding of increased blood pressure; not necessarily hypertensive disorder
Coarctation of aorta
MedGen UID:
341320
Concept ID:
C1848852
Finding
Patent ductus arteriosus
MedGen UID:
504886
Concept ID:
CN001496
Finding
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Aortic valve stenosis
MedGen UID:
504892
Concept ID:
CN001503
Finding
The presence of a stenosis (narrowing) of the aortic valve.
Abnormality of the cardiac septa
MedGen UID:
428275
Concept ID:
CN001520
Finding
An anomaly of the intra-atrial or intraventricular septum.
Pericardial effusion
MedGen UID:
504918
Concept ID:
CN001544
Finding
Accumulation of fluid within the pericardium.
Respiratory insufficiency
MedGen UID:
155440
Concept ID:
C0748358
Finding
Laryngotracheal stenosis
MedGen UID:
812610
Concept ID:
C3806280
Finding
Respiratory failure
MedGen UID:
505385
Concept ID:
CN002603
Finding
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
EMG abnormality
MedGen UID:
99199
Concept ID:
C0476403
Finding
Generalized muscle hypertrophy
MedGen UID:
387991
Concept ID:
C1858125
Finding
Skeletal muscle hypertrophy
MedGen UID:
505580
Concept ID:
CN003354
Finding
Hypertrophy (increase in size) of muscle cells (as opposed to hyperplasia, which refers to an increase in the number of muscle cells).
Camptodactyly
MedGen UID:
507335
Concept ID:
CN180568
Finding
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.
Hernia of the abdominal wall
MedGen UID:
428061
Concept ID:
CN003802
Finding
The presence of a hernia in the abdominal wall.
Camptodactyly
MedGen UID:
507335
Concept ID:
CN180568
Finding
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.
Short finger
MedGen UID:
68683
Concept ID:
C0239594
Finding
2-3 toe syndactyly
MedGen UID:
400146
Concept ID:
C1862857
Finding
Radial deviation of finger
MedGen UID:
473540
Concept ID:
C2178410
Finding
Abnormality of the metaphyses
MedGen UID:
428237
Concept ID:
CN000883
Finding
An abnormality of one or more metaphysis, i.e., of the somewhat wider portion of a long bone that is adjacent to the epiphyseal growth plate and grows during childhood.
Brachydactyly syndrome
MedGen UID:
500899
Concept ID:
CN001088
Finding
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
Short toe
MedGen UID:
500911
Concept ID:
CN001658
Finding
A toe that appears disproportionately short compared to the foot.
Overlapping toe
MedGen UID:
504973
Concept ID:
CN001669
Finding
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest.
Clinodactyly
MedGen UID:
807884
Concept ID:
CN220788
Finding
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).

Recent clinical studies

Etiology

Le Goff C, Michot C, Cormier-Daire V
Clin Genet 2014 Jun;85(6):503-13. Epub 2014 Apr 2 doi: 10.1111/cge.12365. [Epub ahead of print] PMID: 24580733
Le Goff C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):145-53. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31337. [Epub ahead of print] PMID: 22791552

Diagnosis

Asakura Y, Muroya K, Sato T, Kurosawa K, Nishimura G, Adachi M
Am J Med Genet A 2012 Aug;158A(8):1982-6. Epub 2012 Jun 18 doi: 10.1002/ajmg.a.35440. [Epub ahead of print] PMID: 22711472
Al Ageeli E, Mignot C, Afenjar A, Whalen S, Dorison N, Mayer M, Esteva B, Dubern B, Momtchilova M, Le Gargasson JF, Bursztyn J, Héron D
Eur J Med Genet 2012 Oct;55(10):541-7. Epub 2012 Jun 7 doi: 10.1016/j.ejmg.2012.05.006. [Epub ahead of print] PMID: 22683461
McGowan R, Gulati R, McHenry P, Cooke A, Butler S, Keng WT, Murday V, Whiteford M, Dikkers FG, Sikkema-Raddatz B, van Essen T, Tolmie J
Eur J Med Genet 2011 Nov-Dec;54(6):e553-9. Epub 2011 Jul 21 doi: 10.1016/j.ejmg.2011.07.001. [Epub ahead of print] PMID: 21816239
Bachmann-Gagescu R, Hisama FM, Yuen AL
Clin Dysmorphol 2011 Jul;20(3):156-9. doi: 10.1097/MCD.0b013e3283468043. PMID: 21490502
Lindor NM
Am J Med Genet A 2009 Feb 15;149A(4):798-9. doi: 10.1002/ajmg.a.32719. PMID: 19267408

Therapy

Picco P, Naselli A, Pala G, Marsciani A, Buoncompagni A, Martini A
Am J Med Genet A 2013 May;161A(5):1164-6. doi: 10.1002/ajmg.a.35892. PMID: 23610053

Prognosis

Le Goff C, Michot C, Cormier-Daire V
Clin Genet 2014 Jun;85(6):503-13. Epub 2014 Apr 2 doi: 10.1111/cge.12365. [Epub ahead of print] PMID: 24580733

Clinical prediction guides

Le Goff C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):145-53. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31337. [Epub ahead of print] PMID: 22791552
Le Goff C, Mahaut C, Abhyankar A, Le Goff W, Serre V, Afenjar A, Destrée A, di Rocco M, Héron D, Jacquemont S, Marlin S, Simon M, Tolmie J, Verloes A, Casanova JL, Munnich A, Cormier-Daire V
Nat Genet 2011 Dec 11;44(1):85-8. doi: 10.1038/ng.1016. [Epub ahead of print] PMID: 22158539

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