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Wieacker Wolff syndrome(WRWF)

MedGen UID:
163227
Concept ID:
C0796200
Disease or Syndrome
Synonyms: Apraxia, oculomotor, with congenital contractures and muscle atrophy; Contractures of feet, muscle atrophy, and oculomotor apraxia; Mental retardation, X-linked, syndromic 4; Mental retardation, X-linked, with congenital contractures and low fingertip arches; Miles-Carpenter X-linked mental retardation syndrome; Wieacker syndrome; WRWF
Modes of inheritance:
X-linked inheritance
MedGen UID:
66838
Concept ID:
C0241764
Genetic Function
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on the X chromosome.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
not inherited
MedGen UID:
832438
Concept ID:
CN227390
Intellectual Product
Source: Orphanet
Describes a disorder that is not inherited.
X-linked recessive inheritance (HPO, OMIM, Orphanet)
not inherited (Orphanet)
SNOMED CT: Intellectual disability, developmental delay, contracture syndrome (722456001); Foot contracture, muscle atrophy, oculomotor apraxia syndrome (722456001); Wieacker Wolff syndrome (722456001)
 
Gene (location): ZC4H2 (Xq11.2)
OMIM®: 314580
Orphanet: ORPHA3454

Definition

Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013). [from OMIM]

Clinical features

Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
A transient absence of spontaneous respiration.
Arthrogryposis multiplex congenita
MedGen UID:
2455
Concept ID:
C0003886
Finding
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle.
Talipes equinovarus
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).
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Dystonia
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Exotropia
MedGen UID:
4613
Concept ID:
C0015310
Disease or Syndrome
A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
A congenital or traumatic abnormality in which the femoral head slips out of the acetabulum.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Abnormally increased curvature of the thoracic portion of the spine.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature of the lumbar portion of the spinal column.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a "free interval") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Seizures
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Scoliosis
MedGen UID:
21278
Concept ID:
C0037932
Finding
The presence of an abnormal lateral curvature of the spine.
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.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
A finding indicating the complete absence of neurological reflexes.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
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.
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 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).
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
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.
Neonatal respiratory distress
MedGen UID:
163106
Concept ID:
C0852283
Disease or Syndrome
Respiratory difficulty as newborn.
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
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).
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
U-Shaped upper lip vermilion
MedGen UID:
383857
Concept ID:
C1856202
Finding
Gentle upward curve of the upper lip vermilion such that the center is placed well superior to the commissures.
Broad alveolar ridges
MedGen UID:
347470
Concept ID:
C1857500
Finding
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Facial palsy
MedGen UID:
346972
Concept ID:
C1858719
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.
Proximal placement of thumb
MedGen UID:
356033
Concept ID:
C1865572
Finding
Proximal mislocalization of the thumb.
High anterior hairline
MedGen UID:
477667
Concept ID:
C3276036
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Retrognathia
MedGen UID:
488375
Concept ID:
C3494422
Finding
A physical misalignment of the upper (maxilla) and lower (mandibular) jaw bones in which either or both recede relative to the frontal plane of the forehead.
Cerebral atrophy
MedGen UID:
892664
Concept ID:
C4020860
Disease or Syndrome
Global developmental delay
MedGen UID:
892935
Concept ID:
C4020875
Pathologic Function
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Palmar hyperkeratosis
MedGen UID:
869284
Concept ID:
C4023710
Disease or Syndrome
Hyperkeratosis affecting the palm of the hand.
Congenital foot contractures
MedGen UID:
870690
Concept ID:
C4025144
Congenital Abnormality

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWieacker Wolff syndrome
Follow this link to review classifications for Wieacker Wolff syndrome in Orphanet.

Recent clinical studies

Diagnosis

Godfrey ND, Dowlatshahi S, Martin MM, Rothkopf DM
Am J Med Genet A 2018 Jan;176(1):167-170. Epub 2017 Nov 17 doi: 10.1002/ajmg.a.38527. PMID: 29150902
Zanzottera C, Milani D, Alfei E, Rizzo A, D'Arrigo S, Esposito S, Pantaleoni C
Am J Med Genet A 2017 May;173(5):1358-1363. Epub 2017 Mar 27 doi: 10.1002/ajmg.a.38155. PMID: 28345801

Therapy

Zanzottera C, Milani D, Alfei E, Rizzo A, D'Arrigo S, Esposito S, Pantaleoni C
Am J Med Genet A 2017 May;173(5):1358-1363. Epub 2017 Mar 27 doi: 10.1002/ajmg.a.38155. PMID: 28345801

Prognosis

Kondo D, Noguchi A, Takahashi I, Kubota H, Yano T, Sato Y, Toyono M, Sawaishi Y, Takahashi T
Brain Dev 2018 Oct;40(9):760-767. Epub 2018 May 24 doi: 10.1016/j.braindev.2018.05.003. PMID: 29803542
Godfrey ND, Dowlatshahi S, Martin MM, Rothkopf DM
Am J Med Genet A 2018 Jan;176(1):167-170. Epub 2017 Nov 17 doi: 10.1002/ajmg.a.38527. PMID: 29150902

Clinical prediction guides

Kondo D, Noguchi A, Takahashi I, Kubota H, Yano T, Sato Y, Toyono M, Sawaishi Y, Takahashi T
Brain Dev 2018 Oct;40(9):760-767. Epub 2018 May 24 doi: 10.1016/j.braindev.2018.05.003. PMID: 29803542
Godfrey ND, Dowlatshahi S, Martin MM, Rothkopf DM
Am J Med Genet A 2018 Jan;176(1):167-170. Epub 2017 Nov 17 doi: 10.1002/ajmg.a.38527. PMID: 29150902
Zanzottera C, Milani D, Alfei E, Rizzo A, D'Arrigo S, Esposito S, Pantaleoni C
Am J Med Genet A 2017 May;173(5):1358-1363. Epub 2017 Mar 27 doi: 10.1002/ajmg.a.38155. PMID: 28345801

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