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Anauxetic dysplasia 3(ANXD3)

MedGen UID:
1718444
Concept ID:
C5394289
Disease or Syndrome
Synonyms: ANAUXETIC DYSPLASIA 3; ANXD3
 
Gene (location): NEPRO (3q13.2)
 
Monarch Initiative: MONDO:0030019
OMIM®: 618853

Definition

Anauxetic dysplasia-3 (ANXD3) is characterized by severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. Radiographs show short metacarpals, broad middle phalanges, and metaphyseal irregularities. Most patients also exhibit motor and cognitive delays (Narayanan et al., 2019). For a discussion of genetic heterogeneity of anauxetic dysplasia, see ANXD1 (607095). [from OMIM]

Clinical features

From HPO
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.
Trident hand
MedGen UID:
98430
Concept ID:
C0426874
Finding
A hand in which the fingers are of nearly equal length and deflected at the first interphalangeal joint, so as to give a forklike shape consisting of separation of the first and second as well as the third and fourth digits.
Hip subluxation
MedGen UID:
140946
Concept ID:
C0434785
Injury or Poisoning
A partial dislocation of the hip joint, whereby the head of the femur is partially displaced from the socket.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Short middle phalanx of finger
MedGen UID:
337690
Concept ID:
C1846950
Finding
Short (hypoplastic) middle phalanx of finger, affecting one or more fingers.
Broad middle phalanx of finger
MedGen UID:
867025
Concept ID:
C4021383
Anatomical Abnormality
Increased width of the middle phalanx of finger.
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
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.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Spinal cord compression
MedGen UID:
11549
Concept ID:
C0037926
Disease or Syndrome
External mechanical compression of the spinal cord.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Plagiocephaly
MedGen UID:
78562
Concept ID:
C0265529
Congenital Abnormality
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
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.
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Squared iliac bones
MedGen UID:
324963
Concept ID:
C1838186
Finding
A shift from the normally round (convex) appearance of the iliac wing towards a square-like appearance.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
Beaking of vertebral bodies
MedGen UID:
341588
Concept ID:
C1856599
Finding
Anterior tongue-like protrusions of the vertebral bodies.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Thoracolumbar kyphoscoliosis
MedGen UID:
347124
Concept ID:
C1859335
Finding
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
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.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
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.
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.
Broad eyebrow
MedGen UID:
344657
Concept ID:
C1856121
Finding
Regional increase in the width (height) of the eyebrow.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
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.
Oligodontia
MedGen UID:
904670
Concept ID:
C4082304
Congenital Abnormality
The absence of six or more teeth from the normal series by a failure to develop.
Cutis laxa
MedGen UID:
8206
Concept ID:
C0010495
Disease or Syndrome
Wrinkled, redundant, inelastic and sagging skin.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.

Recent clinical studies

Etiology

Remmelzwaal PC, Verhagen MV, Jongbloed JDH, van den Akker PC, Veenstra-Knol HE, Hitzert MM
Am J Med Genet A 2023 Sep;191(9):2440-2445. Epub 2023 Jun 9 doi: 10.1002/ajmg.a.63316. PMID: 37294112
Garcia-Tarodo S, Bottani A, Merlini L, Kaelin A, Schwitzgebel VM, Parvex P, Dayer R, Lascombes P, Korff CM
Eur J Paediatr Neurol 2015 May;19(3):367-71. Epub 2015 Jan 3 doi: 10.1016/j.ejpn.2014.12.016. PMID: 25596067
Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A
Am J Hum Genet 2007 Sep;81(3):519-29. Epub 2007 Aug 6 doi: 10.1086/521034. PMID: 17701897Free PMC Article

Diagnosis

Remmelzwaal PC, Verhagen MV, Jongbloed JDH, van den Akker PC, Veenstra-Knol HE, Hitzert MM
Am J Med Genet A 2023 Sep;191(9):2440-2445. Epub 2023 Jun 9 doi: 10.1002/ajmg.a.63316. PMID: 37294112
Hall CM, Liu B, Haworth A, Reed L, Pryce J, Mansour S
Eur J Med Genet 2021 Mar;64(3):104162. Epub 2021 Feb 7 doi: 10.1016/j.ejmg.2021.104162. PMID: 33567347
Garcia-Tarodo S, Bottani A, Merlini L, Kaelin A, Schwitzgebel VM, Parvex P, Dayer R, Lascombes P, Korff CM
Eur J Paediatr Neurol 2015 May;19(3):367-71. Epub 2015 Jan 3 doi: 10.1016/j.ejpn.2014.12.016. PMID: 25596067
Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A
Am J Hum Genet 2007 Sep;81(3):519-29. Epub 2007 Aug 6 doi: 10.1086/521034. PMID: 17701897Free PMC Article

Prognosis

Garcia-Tarodo S, Bottani A, Merlini L, Kaelin A, Schwitzgebel VM, Parvex P, Dayer R, Lascombes P, Korff CM
Eur J Paediatr Neurol 2015 May;19(3):367-71. Epub 2015 Jan 3 doi: 10.1016/j.ejpn.2014.12.016. PMID: 25596067
Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A
Am J Hum Genet 2007 Sep;81(3):519-29. Epub 2007 Aug 6 doi: 10.1086/521034. PMID: 17701897Free PMC Article

Clinical prediction guides

Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A
Am J Hum Genet 2007 Sep;81(3):519-29. Epub 2007 Aug 6 doi: 10.1086/521034. PMID: 17701897Free PMC Article

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