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Stüve-Wiedemann syndrome 1(STWS1)

MedGen UID:
1803541
Concept ID:
C5676888
Disease or Syndrome
Synonyms: STUVE-WIEDEMANN SYNDROME 1; STWS1
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): LIFR (5p13.1)
 
Monarch Initiative: MONDO:0800043
OMIM®: 601559
Orphanet: ORPHA3206

Definition

Stuve-Wiedemann syndrome is an autosomal recessive disorder characterized by bowing of the long bones and other skeletal anomalies, episodic hyperthermia, respiratory distress, and feeding difficulties usually resulting in early death (Dagoneau et al., 2004). See also 'classic' Schwartz-Jampel syndrome type 1 (SJS1; 255800), a phenotypically similar but genetically distinct disorder caused by mutation in the HSPG2 gene (142461) on chromosome 1p36. Genetic Heterogeneity of Stuve-Wiedemann Syndrome Stuve-Wiedemann syndrome-2 (STWS2; 619751) is caused by mutation in the IL6ST gene (600694) on chromosome 5q11. [from OMIM]

Clinical features

From HPO
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Talipes valgus
MedGen UID:
57757
Concept ID:
C0152236
Congenital Abnormality
Outward turning of the heel, resulting in clubfoot with the person walking on the inner part of the foot.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Ulnar deviation of finger
MedGen UID:
68543
Concept ID:
C0231679
Finding
Bending or curvature of a finger toward the ulnar side (i.e., away from the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Thumbs, congenital Clasped
MedGen UID:
98140
Concept ID:
C0431886
Congenital Abnormality
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
Absent patellar reflexes
MedGen UID:
643630
Concept ID:
C0558844
Finding
Absence of the knee jerk reflex, which can normally be elicited by tapping the patellar tendon with a reflex hammer just below the patella.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Talipes
MedGen UID:
220976
Concept ID:
C1301937
Congenital Abnormality
A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus.
Flexion contracture of toe
MedGen UID:
237248
Concept ID:
C1406835
Finding
One or more bent (flexed) toe joints that cannot be straightened actively or passively.
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
Pulmonary arterial medial hypertrophy
MedGen UID:
306155
Concept ID:
C1504382
Disease or Syndrome
Increase in mass of the tunica media of the arteries in the pulmonary circulation.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
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.
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).
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
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.
Abnormal autonomic nervous system physiology
MedGen UID:
8511
Concept ID:
C0013363
Disease or Syndrome
A functional abnormality of the autonomic nervous system.
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.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
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.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
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.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
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.
Myotonia
MedGen UID:
675119
Concept ID:
C0700153
Finding
An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.
Metaphyseal rarefaction
MedGen UID:
371259
Concept ID:
C1832146
Finding
Reduction in density of metaphyseal bony tissue.
Diaphyseal undertubulation
MedGen UID:
331984
Concept ID:
C1835473
Finding
Tubulation refers to the size and shape of tubular bones. In children and adolescents, the modeling process regulates normal bone growth. Final shaft (tube) diameter depends on appositional bone growth and the equilibrium between periosteal and endosteal bone resorption and formation. Undertubulation refers to a broad, widened form of the shafts (diaphyses) of long bones.
Broad ischia
MedGen UID:
324622
Concept ID:
C1836868
Finding
Increased width of the ischium, which forms the lower and back part of the hip bone.
Thickened cortex of long bones
MedGen UID:
333557
Concept ID:
C1840418
Finding
Abnormal thickening of the cortex of long bones.
Hypoplastic iliac body
MedGen UID:
376500
Concept ID:
C1849034
Finding
Underdevelopment of the body of ilium.
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Bowing of the long bones
MedGen UID:
340849
Concept ID:
C1855340
Congenital Abnormality
A bending or abnormal curvature of a long bone.
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Abnormal metaphyseal trabeculation
MedGen UID:
387751
Concept ID:
C1857139
Finding
An abnormality of the pattern of trabecula (small interconnecting rods of bone) in a metaphyseal region of bone.
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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Enlarged joints
MedGen UID:
347068
Concept ID:
C1859111
Finding
Increase in size of one or more joints.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Contracture of the proximal interphalangeal joint of the 5th finger
MedGen UID:
767526
Concept ID:
C3554612
Finding
Proximal interphalangeal (PIP) flexion deformity of the little finger. That is, the PIP joint of a little finger is bent (flexed) and cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
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.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Abnormality of temperature regulation
MedGen UID:
330395
Concept ID:
C1832160
Finding
An abnormality of temperature homeostasis.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Hypernasal speech
MedGen UID:
99115
Concept ID:
C0454555
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Smooth tongue
MedGen UID:
510156
Concept ID:
C0155964
Disease or Syndrome
Glossy appearance of the entire tongue surface.
Short palpebral fissure
MedGen UID:
98067
Concept ID:
C0423112
Finding
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Square face
MedGen UID:
371253
Concept ID:
C1832127
Finding
Facial contours, as viewed from the front, show a broad upper face/cranium and lower face/mandible, creating a square appearance.
Pursed lips
MedGen UID:
371254
Concept ID:
C1832130
Finding
An abnormality of the appearance of the face caused by constant contraction of the lips leading to a puckered or pursed appearance.
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).
Wide nasal base
MedGen UID:
341506
Concept ID:
C1849667
Finding
Increased distance between the attachments of the alae nasi to the face.
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.
Low hanging columella
MedGen UID:
344656
Concept ID:
C1856119
Finding
Columella extending inferior to the level of the nasal base, when viewed from the side.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Premature skin wrinkling
MedGen UID:
19996
Concept ID:
C0037301
Finding
The presence of an increased degree of wrinkling (irregular folds and indentations) of the skin as compared with age-related norms.
Milia
MedGen UID:
87528
Concept ID:
C0345996
Anatomical Abnormality
Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Blotching pigmentation of the skin
MedGen UID:
870386
Concept ID:
C4024831
Finding
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Decreased lacrimation
MedGen UID:
116004
Concept ID:
C0235857
Finding
Abnormally decreased lacrimation, that is, reduced ability to produce tears.
Absent corneal reflex
MedGen UID:
78835
Concept ID:
C0278211
Finding
Absence of the corneal blinking reflex, which normally induces involuntary blinking of the eyelids following contact of the cornea. The corneal blink reflex is caused by a loop between the trigeminal sensory nerves and the facial motor (VII) nerve innervation of the orbicularis oculi muscles.
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.

Professional guidelines

PubMed

Injarie AM, Narang A, Idrees Z, Saggar AK, Nischal KK
Cornea 2012 Mar;31(3):269-72. doi: 10.1097/ICO.0b013e3182182089. PMID: 22316651

Recent clinical studies

Etiology

Chen YH, van Zon S, Adams A, Schmidt-Arras D, Laurence ADJ, Uhlig HH
J Clin Immunol 2023 Dec 22;44(1):30. doi: 10.1007/s10875-023-01603-7. PMID: 38133879Free PMC Article
Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article
Guran T, Guran O, Paketci C, Kipoglu O, Firat I, Turan S, Atay Z, Haliloglu B, Bereket A
Pituitary 2015 Aug;18(4):456-60. doi: 10.1007/s11102-014-0594-5. PMID: 25145448
Injarie AM, Narang A, Idrees Z, Saggar AK, Nischal KK
Cornea 2012 Mar;31(3):269-72. doi: 10.1097/ICO.0b013e3182182089. PMID: 22316651
Cormier-Daire V, Geneviève D, Munnich A, Le Merrer M
Clin Genet 2004 Sep;66(3):169-76. doi: 10.1111/j.0009-9163.2004.00307.x. PMID: 15324311

Diagnosis

Cores ML, de Los Bueis AB
Rom J Ophthalmol 2023 Oct-Dec;67(4):412-415. doi: 10.22336/rjo.2023.66. PMID: 38239413Free PMC Article
McDermott H, Simmonds J, Thyagarajan M; Genomics England Research Consortium, Islam L, Naik S, Titheradge H
Eur J Med Genet 2023 Aug;66(8):104788. Epub 2023 Jun 7 doi: 10.1016/j.ejmg.2023.104788. PMID: 37295610
Rugolo S, Cavallaro A, Giuffrida L, Cianci A
Minerva Ginecol 2007 Feb;59(1):91-4. PMID: 17353878
Kozlowski K, Tenconi R
Am J Med Genet 1996 May 3;63(1):17-9. doi: 10.1002/(SICI)1096-8628(19960503)63:1<17::AID-AJMG6>3.0.CO;2-P. PMID: 8723081

Therapy

Chen YH, Zastrow DB, Metcalfe RD, Gartner L, Krause F, Morton CJ, Marwaha S, Fresard L, Huang Y, Zhao C, McCormack C, Bick D, Worthey EA, Eng CM, Gold J, Undiagnosed Diseases Network, Montgomery SB, Fisher PG, Ashley EA, Wheeler MT, Parker MW, Shanmugasundaram V, Putoczki TL, Schmidt-Arras D, Laurence A, Bernstein JA, Griffin MDW, Uhlig HH
J Allergy Clin Immunol 2021 Aug;148(2):585-598. Epub 2021 Mar 23 doi: 10.1016/j.jaci.2021.02.044. PMID: 33771552
Injarie AM, Narang A, Idrees Z, Saggar AK, Nischal KK
Cornea 2012 Mar;31(3):269-72. doi: 10.1097/ICO.0b013e3182182089. PMID: 22316651
Crisponi L, Crisponi G, Meloni A, Toliat MR, Nurnberg G, Usala G, Uda M, Masala M, Hohne W, Becker C, Marongiu M, Chiappe F, Kleta R, Rauch A, Wollnik B, Strasser F, Reese T, Jakobs C, Kurlemann G, Cao A, Nurnberg P, Rutsch F
Am J Hum Genet 2007 May;80(5):971-81. Epub 2007 Mar 30 doi: 10.1086/516843. PMID: 17436252Free PMC Article
Dagoneau N, Bellais S, Blanchet P, Sarda P, Al-Gazali LI, Di Rocco M, Huber C, Djouadi F, Le Goff C, Munnich A, Cormier-Daire V
Am J Hum Genet 2007 May;80(5):966-70. Epub 2007 Mar 13 doi: 10.1086/513608. PMID: 17436251Free PMC Article

Prognosis

Chen YH, van Zon S, Adams A, Schmidt-Arras D, Laurence ADJ, Uhlig HH
J Clin Immunol 2023 Dec 22;44(1):30. doi: 10.1007/s10875-023-01603-7. PMID: 38133879Free PMC Article
Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article
Injarie AM, Narang A, Idrees Z, Saggar AK, Nischal KK
Cornea 2012 Mar;31(3):269-72. doi: 10.1097/ICO.0b013e3182182089. PMID: 22316651
Nannenberg EA, Bijlmer R, Van Geel BM, Hennekam RC
Am J Med Genet A 2005 Feb 15;133A(1):90-2. doi: 10.1002/ajmg.a.30536. PMID: 15637710
Al-Gazali LI, Ravenscroft A, Feng A, Shubbar A, Al-Saggaf A, Haas D
Clin Dysmorphol 2003 Jan;12(1):1-8. doi: 10.1097/00019605-200301000-00001. PMID: 12514358

Clinical prediction guides

Chen YH, van Zon S, Adams A, Schmidt-Arras D, Laurence ADJ, Uhlig HH
J Clin Immunol 2023 Dec 22;44(1):30. doi: 10.1007/s10875-023-01603-7. PMID: 38133879Free PMC Article
Dagoneau N, Bellais S, Blanchet P, Sarda P, Al-Gazali LI, Di Rocco M, Huber C, Djouadi F, Le Goff C, Munnich A, Cormier-Daire V
Am J Hum Genet 2007 May;80(5):966-70. Epub 2007 Mar 13 doi: 10.1086/513608. PMID: 17436251Free PMC Article
Dagoneau N, Scheffer D, Huber C, Al-Gazali LI, Di Rocco M, Godard A, Martinovic J, Raas-Rothschild A, Sigaudy S, Unger S, Nicole S, Fontaine B, Taupin JL, Moreau JF, Superti-Furga A, Le Merrer M, Bonaventure J, Munnich A, Legeai-Mallet L, Cormier-Daire V
Am J Hum Genet 2004 Feb;74(2):298-305. Epub 2004 Jan 21 doi: 10.1086/381715. PMID: 14740318Free PMC Article

Recent systematic reviews

Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article

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