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Noonan syndrome 7(NS7)

MedGen UID:
462320
Concept ID:
C3150970
Disease or Syndrome
Synonyms: BRAF-Related Noonan Syndrome; NS7
 
Gene (location): BRAF (7q34)
 
Monarch Initiative: MONDO:0013379
OMIM®: 613706

Disease characteristics

Excerpted from the GeneReview: Noonan Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population. [from GeneReviews]
Authors:
Amy E Roberts   view full author information

Additional descriptions

From OMIM
Noonan syndrome-7 (NS7) is a developmental disorder characterized by reduced postnatal growth, dysmorphic facial features, cardiac defects, and variable cognitive defects (summary by Sarkozy et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).  http://www.omim.org/entry/613706
From MedlinePlus Genetics
Noonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.

People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck.

Between 50 and 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually a normal length and weight, but growth slows over time. Abnormal levels of growth hormone, a protein that is necessary for the normal growth of the body's bones and tissues, may contribute to the slow growth.

Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis).

Most people with Noonan syndrome have some form of critical congenital heart disease. The most common heart defect in these individuals is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some have hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle.

A variety of bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Rarely, women with Noonan syndrome who have a bleeding disorder have excessive bleeding during menstruation (menorrhagia) or childbirth.

Adolescent males with Noonan syndrome typically experience delayed puberty. They go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt that results in shortened stature. Most males with Noonan syndrome have undescended testes (cryptorchidism), which may contribute to infertility (inability to father a child) later in life. Females with Noonan syndrome can experience delayed puberty but most have normal puberty and fertility.

Noonan syndrome is one of a group of related conditions, collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome, the RASopathies include cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, Legius syndrome, and Noonan syndrome with multiple lentigines.

Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a few have special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Affected infants may have feeding problems, which typically get better by age 1 or 2 years. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Older individuals can also develop lymphedema, usually in the ankles and lower legs.

Some people with Noonan syndrome develop cancer, particularly those involving the blood-forming cells (leukemia). It has been estimated that children with Noonan syndrome have an eightfold increased risk of developing leukemia or other cancers over age-matched peers.  https://medlineplus.gov/genetics/condition/noonan-syndrome

Clinical features

From HPO
Lentigo maligna melanoma
MedGen UID:
439437
Concept ID:
C2739810
Neoplastic Process
A subtype of melanoma in situ that typically develops on sun-damaged skin. The lesion is typically a large, irregularly pigmented macule that has developed from an ordinary lentigo (a small pigmented spot on the skin with a clearly-defined edge). Change to a malignant lentigo typically takes place over 20 years or more, and many patients accept the change as a consequence of aging.
Cubitus valgus
MedGen UID:
490152
Concept ID:
C0158465
Acquired Abnormality
Abnormal positioning in which the elbows are turned out.
Deep palmar crease
MedGen UID:
387849
Concept ID:
C1857539
Finding
Excessively deep creases of the palm.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
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).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Abnormal esophagus morphology
MedGen UID:
539700
Concept ID:
C0266126
Congenital Abnormality
A structural abnormality of the esophagus.
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Nasogastric tube feeding in infancy
MedGen UID:
868930
Concept ID:
C4023343
Finding
Feeding problem necessitating nasogastric tube feeding.
Impaired oropharyngeal swallow response
MedGen UID:
1380475
Concept ID:
C4477013
Finding
Delay or absence of the swallow response, reflexes triggered by the contact the food bolus makes with the anterior faucial pillars.
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.
Thickened helices
MedGen UID:
325240
Concept ID:
C1837732
Finding
Increased thickness of the helix of the ear.
Large earlobe
MedGen UID:
334979
Concept ID:
C1844573
Finding
Increased volume of the earlobe, that is, abnormally prominent ear lobules.
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.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
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.
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.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Shield chest
MedGen UID:
322348
Concept ID:
C1834124
Finding
A broad chest.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Webbed neck
MedGen UID:
113154
Concept ID:
C0221217
Congenital Abnormality
Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
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).
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 vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Low posterior hairline
MedGen UID:
383755
Concept ID:
C1855728
Finding
Hair on the neck extends more inferiorly than usual.
Abnormality of the chin
MedGen UID:
871368
Concept ID:
C4025864
Anatomical Abnormality
An abnormality of the chin, i.e., of the inferior portion of the face lying inferior to the lower lip and including the central prominence of the lower jaw.
Palpebral thickening
MedGen UID:
1369577
Concept ID:
C4476868
Finding
An increased thickness of the eyelid not related to acute inflammation.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Curly hair
MedGen UID:
488919
Concept ID:
C0558165
Finding
Numerous nevi
MedGen UID:
341508
Concept ID:
C1849677
Finding
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).
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.

Professional guidelines

PubMed

Tillmann V, Patel L, Gill MS, Whatmore AJ, Price DA, Kibirige MS, Wales JK, Clayton PE
Clin Endocrinol (Oxf) 2000 Sep;53(3):329-36. doi: 10.1046/j.1365-2265.2000.01105.x. PMID: 10971450

Recent clinical studies

Etiology

Swarts JW, Kleimeier LER, Leenders EKSM, Rinne T, Klein WM, Draaisma JMT
Am J Med Genet A 2022 Nov;188(11):3242-3261. Epub 2022 Aug 18 doi: 10.1002/ajmg.a.62955. PMID: 35979676Free PMC Article
PHOSP-COVID Collaborative Group
Lancet Respir Med 2022 Aug;10(8):761-775. Epub 2022 Apr 23 doi: 10.1016/S2213-2600(22)00127-8. PMID: 35472304Free PMC Article
Mohan P, Lemoine J, Trotter C, Rakova I, Billings P, Peacock S, Kao CY, Wang Y, Xia F, Eng CM, Benn P
Ultrasound Obstet Gynecol 2022 Jan;59(1):33-39. doi: 10.1002/uog.23756. PMID: 34358384Free PMC Article
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Bavle A, Shah R, Gross N, Gavula T, Ruiz-Elizalde A, Wierenga K, McNall-Knapp R
J Pediatr Hematol Oncol 2018 Oct;40(7):553-554. doi: 10.1097/MPH.0000000000001170. PMID: 29683947

Diagnosis

Swarts JW, Kleimeier LER, Leenders EKSM, Rinne T, Klein WM, Draaisma JMT
Am J Med Genet A 2022 Nov;188(11):3242-3261. Epub 2022 Aug 18 doi: 10.1002/ajmg.a.62955. PMID: 35979676Free PMC Article
Mohan P, Lemoine J, Trotter C, Rakova I, Billings P, Peacock S, Kao CY, Wang Y, Xia F, Eng CM, Benn P
Ultrasound Obstet Gynecol 2022 Jan;59(1):33-39. doi: 10.1002/uog.23756. PMID: 34358384Free PMC Article
Leach NT, Wilson Mathews DR, Rosenblum LS, Zhou Z, Zhu H, Heim RA
Genet Med 2019 Feb;21(2):417-425. Epub 2018 Jun 15 doi: 10.1038/s41436-018-0062-0. PMID: 29907801
Bavle A, Shah R, Gross N, Gavula T, Ruiz-Elizalde A, Wierenga K, McNall-Knapp R
J Pediatr Hematol Oncol 2018 Oct;40(7):553-554. doi: 10.1097/MPH.0000000000001170. PMID: 29683947
Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, Torrrente I, Selicorni A, Mazzanti L, Digilio MC, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M
Hum Mutat 2011 Jul;32(7):760-72. Epub 2011 Apr 28 doi: 10.1002/humu.21492. PMID: 21387466Free PMC Article

Therapy

Wu X, Wu J, Yuan Y, Yang L, Yu L
Mol Genet Genomic Med 2023 Nov;11(11):e2266. Epub 2023 Aug 1 doi: 10.1002/mgg3.2266. PMID: 37525886Free PMC Article
Pittet LF, Messina NL, Orsini F, Moore CL, Abruzzo V, Barry S, Bonnici R, Bonten M, Campbell J, Croda J, Dalcolmo M, Gardiner K, Gell G, Germano S, Gomes-Silva A, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Lacerda MVG, Lee KJ, Lucas M, Lynn DJ, Manning L, Marshall HS, McDonald E, Munns CF, Nicholson S, O'Connell A, de Oliveira RD, Perlen S, Perrett KP, Prat-Aymerich C, Richmond PC, Rodriguez-Baño J, Dos Santos G, da Silva PV, Teo JW, Villanueva P, Warris A, Wood NJ, Davidson A, Curtis N; BRACE Trial Consortium Group
N Engl J Med 2023 Apr 27;388(17):1582-1596. doi: 10.1056/NEJMoa2212616. PMID: 37099341Free PMC Article
Webster ALH, Sanders MA, Patel K, Dietrich R, Noonan RJ, Lach FP, White RR, Goldfarb A, Hadi K, Edwards MM, Donovan FX, Hoogenboezem RM, Jung M, Sridhar S, Wiley TF, Fedrigo O, Tian H, Rosiene J, Heineman T, Kennedy JA, Bean L, Rosti RO, Tryon R, Gonzalez AM, Rosenberg A, Luo JD, Carroll TS, Shroff S, Beaumont M, Velleuer E, Rastatter JC, Wells SI, Surrallés J, Bagby G, MacMillan ML, Wagner JE, Cancio M, Boulad F, Scognamiglio T, Vaughan R, Beaumont KG, Koren A, Imielinski M, Chandrasekharappa SC, Auerbach AD, Singh B, Kutler DI, Campbell PJ, Smogorzewska A
Nature 2022 Dec;612(7940):495-502. Epub 2022 Nov 30 doi: 10.1038/s41586-022-05253-4. PMID: 36450981Free PMC Article
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Bavle A, Shah R, Gross N, Gavula T, Ruiz-Elizalde A, Wierenga K, McNall-Knapp R
J Pediatr Hematol Oncol 2018 Oct;40(7):553-554. doi: 10.1097/MPH.0000000000001170. PMID: 29683947

Prognosis

Boleti O, Norrish G, Field E, Dady K, Summers K, Nepali G, Bhole V, Uzun O, Wong A, Daubeney PEF, Stuart G, Fernandes P, McLeod K, Ilina M, Ali MNL, Bharucha T, Donne GD, Brown E, Linter K, Jones CB, Searle J, Regan W, Mathur S, Boyd N, Reinhardt Z, Duignan S, Prendiville T, Adwani S, Kaski JP
ESC Heart Fail 2024 Apr;11(2):923-936. Epub 2024 Jan 13 doi: 10.1002/ehf2.14637. PMID: 38217456Free PMC Article
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Eur J Pediatr 2022 Aug;181(8):2919-2926. Epub 2022 May 16 doi: 10.1007/s00431-022-04497-6. PMID: 35575813
Magoulas PL, El-Hattab AW
Orphanet J Rare Dis 2012 Jan 4;7:2. doi: 10.1186/1750-1172-7-2. PMID: 22216833Free PMC Article
Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, Torrrente I, Selicorni A, Mazzanti L, Digilio MC, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M
Hum Mutat 2011 Jul;32(7):760-72. Epub 2011 Apr 28 doi: 10.1002/humu.21492. PMID: 21387466Free PMC Article
Sarkozy A, Digilio MC, Dallapiccola B
Orphanet J Rare Dis 2008 May 27;3:13. doi: 10.1186/1750-1172-3-13. PMID: 18505544Free PMC Article

Clinical prediction guides

PHOSP-COVID Collaborative Group
Lancet Respir Med 2022 Aug;10(8):761-775. Epub 2022 Apr 23 doi: 10.1016/S2213-2600(22)00127-8. PMID: 35472304Free PMC Article
Mohan P, Lemoine J, Trotter C, Rakova I, Billings P, Peacock S, Kao CY, Wang Y, Xia F, Eng CM, Benn P
Ultrasound Obstet Gynecol 2022 Jan;59(1):33-39. doi: 10.1002/uog.23756. PMID: 34358384Free PMC Article
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Leach NT, Wilson Mathews DR, Rosenblum LS, Zhou Z, Zhu H, Heim RA
Genet Med 2019 Feb;21(2):417-425. Epub 2018 Jun 15 doi: 10.1038/s41436-018-0062-0. PMID: 29907801
Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, Cordeddu V, Williams BJ, Dentici ML, Caputo V, Venanzi S, Bonaguro M, Kavamura I, Faienza MF, Pilotta A, Stanzial F, Faravelli F, Gabrielli O, Marino B, Neri G, Silengo MC, Ferrero GB, Torrrente I, Selicorni A, Mazzanti L, Digilio MC, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M
Hum Mutat 2011 Jul;32(7):760-72. Epub 2011 Apr 28 doi: 10.1002/humu.21492. PMID: 21387466Free PMC Article

Recent systematic reviews

Cavoretto PI, Castoldi M, Corbella G, Forte A, Moharamzadeh D, Emedoli D, Candiani M, De Pellegrin M
Ultrasound Obstet Gynecol 2023 Dec;62(6):778-787. doi: 10.1002/uog.26283. PMID: 37289939
Cox TP, Vance CJ, Daley SK, Papendieck C, McGregor H, Kuo P, Witte MH
J Vasc Surg Venous Lymphat Disord 2022 Sep;10(5):1192-1196.e3. Epub 2022 May 10 doi: 10.1016/j.jvsv.2022.03.017. PMID: 35561969Free PMC Article
Bader-Meunier B, Cavé H, Jeremiah N, Magerus A, Lanzarotti N, Rieux-Laucat F, Cormier-Daire V
Semin Arthritis Rheum 2013 Oct;43(2):217-9. Epub 2013 Jun 17 doi: 10.1016/j.semarthrit.2013.04.009. PMID: 23786871

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