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Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome(PSACH)

MedGen UID:
98378
Concept ID:
C0410538
Congenital Abnormality
Synonyms: PSACH; Pseudoachondroplasia; Pseudoachondroplastic dysplasia; Pseudoachondroplastic spondyloepiphyseal dysplasia
SNOMED CT: Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome (22567005); SED syndrome (22567005); Pseudoachondroplastic dysplasia (22567005); Pseudoachondroplasia (22567005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): COMP (19p13.11)
 
Monarch Initiative: MONDO:0008322
OMIM®: 177170
Orphanet: ORPHA750

Disease characteristics

Excerpted from the GeneReview: COMP-Related Pseudoachondroplasia
COMP-related pseudoachondroplasia (COMP-PSACH) is characterized by normal length at birth and normal facies. Often the presenting feature is a waddling gait, recognized at the onset of walking. Typically, the growth rate falls below the standard growth curve by approximately age two years, leading to a moderately severe form of disproportionate short-limb short stature. Joint pain during childhood, particularly in the large joints of the lower extremities, is common. Degenerative joint disease is progressive; approximately 50% of individuals with COMP-PSACH eventually require hip replacement surgery. [from GeneReviews]
Authors:
Michael D Briggs  |  Michael J Wright   view full author information

Additional descriptions

From OMIM
Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia characterized by disproportionate short stature, deformity of the lower limbs, brachydactyly, loose joints, and ligamentous laxity. Vertebral anomalies, present in childhood, usually resolve with age, but osteoarthritis is progressive and severe. PSACH and EDM1 comprise a clinical spectrum with phenotypic overlap between mild forms of PSACH and EDM1 (summary by Briggs and Chapman, 2002).  http://www.omim.org/entry/177170
From MedlinePlus Genetics
Pseudoachondroplasia is an inherited disorder of bone growth. It was once thought to be related to another disorder of bone growth called achondroplasia, but without that disorder's characteristic facial features. More research has demonstrated that pseudoachondroplasia is a separate disorder.

All people with pseudoachondroplasia have short stature. The average height of adult males with this condition is 120 centimeters (3 feet, 11 inches), and the average height of adult females is 116 centimeters (3 feet, 9 inches). Individuals with pseudoachondroplasia are not unusually short at birth; by the age of two, their growth rate falls below the standard growth curve.

Other characteristic features of pseudoachondroplasia include short arms and legs; a waddling walk; joint pain in childhood that progresses to a joint disease known as osteoarthritis; an unusually large range of joint movement (hyperextensibility) in the hands, knees, and ankles; and a limited range of motion at the elbows and hips. Some people with pseudoachondroplasia have legs that turn outward or inward (valgus or varus deformity). Sometimes, one leg turns outward and the other inward, which is called windswept deformity. Some affected individuals have a spine that curves to the side (scoliosis) or an abnormally curved lower back (lordosis). People with pseudoachondroplasia have normal facial features, head size, and intelligence.  https://medlineplus.gov/genetics/condition/pseudoachondroplasia

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
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 the wrist
MedGen UID:
115906
Concept ID:
C0231678
Sign or Symptom
Ulnar deviation of the hand
MedGen UID:
66031
Concept ID:
C0241521
Finding
Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger).
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
Genu recurvatum
MedGen UID:
107486
Concept ID:
C0546964
Anatomical Abnormality
An abnormally increased extension of the knee joint, so that the knee can bend backwards.
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 phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
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 distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Carpal bone hypoplasia
MedGen UID:
355049
Concept ID:
C1863749
Finding
Underdevelopment of one or more carpal bones.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Ulnar metaphyseal irregularity
MedGen UID:
867324
Concept ID:
C4021688
Anatomical Abnormality
Irregularity of the normally smooth surface of the metaphysis of the ulna.
Radial metaphyseal irregularity
MedGen UID:
867328
Concept ID:
C4021692
Anatomical Abnormality
Irregularity of the normally smooth surface of the metaphysis of the radius.
Irregular carpal bones
MedGen UID:
870939
Concept ID:
C4025401
Anatomical Abnormality
Carpal bones with irregular or fragmented margins.
Disproportionate short-limb short stature
MedGen UID:
342370
Concept ID:
C1849937
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Childhood onset short-limb short stature
MedGen UID:
357998
Concept ID:
C1867487
Finding
Sensory neuropathy
MedGen UID:
101791
Concept ID:
C0151313
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Cervical cord compression
MedGen UID:
167271
Concept ID:
C0852866
Finding
Compression of the spinal cord in the cervical region, generally manifested by paresthesias and numbness, weakness, difficulty walking, abnormalities of coordination, and neck pain or stiffness.
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.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Osteoarthritis
MedGen UID:
45244
Concept ID:
C0029408
Disease or Syndrome
Osteoarthritis (OA) is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis (Meulenbelt et al., 2006). Clinical problems include pain and joint stiffness often leading to significant disability and joint replacement. Osteoarthritis exhibits a clear predilection for specific joints; it appears most commonly in the hip and knee joints and lumbar and cervical spine, as well as in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints of the hand; however, patients with osteoarthritis may have 1, a few, or all of these sites affected (Stefansson et al., 2003). According to a conservative estimate, greater than 70% of the population of the United States at age 65 years is affected by the disease, reflecting its age dependence. Genetic Heterogeneity of Susceptibility to Osteoarthritis Susceptibility to osteoarthritis has been associated with variation in other genes: OS2 (140600) with variation in the MATN3 gene (602109) on chromosome 2p24; OS3 (607850) with variation in the ASPN gene (608135) on chromosome 9q22; and OS5 (612400) with variation in the GDF5 gene (601146) on chromosome 20q11. Other susceptibility loci for osteoarthritis have been mapped to chromosomes 2q33 (OS4; 610839) and 3p24 (OS6; 612401).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Atlantoaxial dislocation
MedGen UID:
82672
Concept ID:
C0263905
Injury or Poisoning
Partial dislocation of the atlantoaxial joint.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
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.
Odontoid hypoplasia
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Irregular epiphyses
MedGen UID:
337584
Concept ID:
C1846449
Finding
An alteration of the normally smooth contour of the epiphysis leading to an irregular appearance.
Small epiphyses
MedGen UID:
339612
Concept ID:
C1846803
Finding
Reduction in the size or volume of epiphyses.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Limited shoulder movement
MedGen UID:
341979
Concept ID:
C1851313
Finding
A limitation of the range of movement of the shoulder joint.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Beaking of vertebral bodies
MedGen UID:
341588
Concept ID:
C1856599
Finding
Anterior tongue-like protrusions of the vertebral bodies.
Spatulate ribs
MedGen UID:
344777
Concept ID:
C1856637
Finding
Ribs that are increased in width and taper to the posterior ends.
Delayed epiphyseal ossification
MedGen UID:
351324
Concept ID:
C1865200
Finding
Fragmented, irregular epiphyses
MedGen UID:
357293
Concept ID:
C1867494
Finding
Limited hip extension
MedGen UID:
766282
Concept ID:
C3553368
Finding
Limitation of the extension of the hip, i.e., decreased ability to straighten the hip joint and thereby increase the angle between torso and thigh; moving the thigh or top of the pelvis backward.
Small epiphyses of the phalanges of the hand
MedGen UID:
866949
Concept ID:
C4021305
Anatomical Abnormality
Abnormally small size of the epiphyses of the phalanges of the fingers with respect to age-dependent norms.
Fragmented epiphyses
MedGen UID:
867862
Concept ID:
C4022253
Anatomical Abnormality
Fragmented appearance of the epiphyses.
Flared femoral metaphysis
MedGen UID:
871197
Concept ID:
C4025674
Anatomical Abnormality

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPseudoachondroplastic spondyloepiphyseal dysplasia syndrome
Follow this link to review classifications for Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome in Orphanet.

Professional guidelines

PubMed

Jacob P, Bhavani GSL, Shah H, Galada C, Nampoothiri S, Kamath N, Phadke SR, Muranjan M, Datar CA, Shukla A, Girisha KM
Am J Med Genet A 2022 Mar;188(3):751-759. Epub 2021 Nov 9 doi: 10.1002/ajmg.a.62566. PMID: 34750995
Kennedy J, Jackson G, Ramsden S, Taylor J, Newman W, Wright MJ, Donnai D, Elles R, Briggs MD
Eur J Hum Genet 2005 May;13(5):547-55. doi: 10.1038/sj.ejhg.5201374. PMID: 15756302Free PMC Article
Briggs MD, Chapman KL
Hum Mutat 2002 May;19(5):465-78. doi: 10.1002/humu.10066. PMID: 11968079

Recent clinical studies

Etiology

Briggs MD, Bell PA, Pirog KA
Int J Mol Med 2015 Jun;35(6):1483-92. Epub 2015 Mar 30 doi: 10.3892/ijmm.2015.2158. PMID: 25824717Free PMC Article
Tunkel D, Alade Y, Kerbavaz R, Smith B, Rose-Hardison D, Hoover-Fong J
Am J Med Genet A 2012 Jul;158A(7):1551-5. Epub 2012 May 24 doi: 10.1002/ajmg.a.35373. PMID: 22628261
McKay SD, Al-Omari A, Tomlinson LA, Dormans JP
Spine (Phila Pa 1976) 2012 Mar 1;37(5):E269-77. doi: 10.1097/BRS.0b013e31823b3ded. PMID: 22045003
Tolo VT
Instr Course Lect 1990;39:399-405. PMID: 2186130
Kaitila I, Leisti JT, Rimoin DL
Clin Orthop Relat Res 1976 Jan-Feb;(114):94-106. PMID: 1261139

Diagnosis

Jacob P, Bhavani GSL, Shah H, Galada C, Nampoothiri S, Kamath N, Phadke SR, Muranjan M, Datar CA, Shukla A, Girisha KM
Am J Med Genet A 2022 Mar;188(3):751-759. Epub 2021 Nov 9 doi: 10.1002/ajmg.a.62566. PMID: 34750995
McKay SD, Al-Omari A, Tomlinson LA, Dormans JP
Spine (Phila Pa 1976) 2012 Mar 1;37(5):E269-77. doi: 10.1097/BRS.0b013e31823b3ded. PMID: 22045003
Khungar A, Mahajan P, Gupte G, Vasundhara M, Kher A, Bharucha BA
J Postgrad Med 1993 Apr-Jun;39(2):91-3. PMID: 8169872
Tolo VT
Instr Course Lect 1990;39:399-405. PMID: 2186130
Stanescu V, Stanescu R, Maroteaux P
J Bone Joint Surg Am 1984 Jul;66(6):817-36. doi: 10.2106/00004623-198466060-00002. PMID: 6376516

Therapy

Guo BB, Jin JY, Yuan ZZ, Zeng L, Xiang R
Biomed Res Int 2021;2021:6678531. Epub 2021 Mar 8 doi: 10.1155/2021/6678531. PMID: 33748277Free PMC Article
Raggio CL, Yonko EA, Khan SI, Carter EM, Citron KP, Bostrom MPG, Figgie MP
J Arthroplasty 2020 Aug;35(8):1993-2001. Epub 2020 Apr 9 doi: 10.1016/j.arth.2020.04.007. PMID: 32386881
Pesenti S, Iobst CA, Launay F
Orthop Traumatol Surg Res 2017 Sep;103(5):761-764. Epub 2017 Apr 17 doi: 10.1016/j.otsr.2017.03.015. PMID: 28428035
Wilczynska M, Ching T
BMJ Case Rep 2011 Oct 11;2011 doi: 10.1136/bcr.08.2011.4667. PMID: 22675014Free PMC Article
Kanazawa H, Tanaka H, Inoue M, Yamanaka Y, Namba N, Seino Y
J Bone Miner Metab 2003;21(5):307-10. doi: 10.1007/s00774-003-0425-7. PMID: 12928832

Prognosis

Posey KL, Coustry F, Hecht JT
Matrix Biol 2018 Oct;71-72:161-173. Epub 2018 Mar 9 doi: 10.1016/j.matbio.2018.02.023. PMID: 29530484Free PMC Article
Briggs MD, Brock J, Ramsden SC, Bell PA
Eur J Hum Genet 2014 Nov;22(11):1278-82. Epub 2014 Mar 5 doi: 10.1038/ejhg.2014.30. PMID: 24595329Free PMC Article
Posey KL, Hecht JT
Curr Drug Targets 2008 Oct;9(10):869-77. doi: 10.2174/138945008785909293. PMID: 18855621
Stanescu V, Stanescu R, Maroteaux P
J Bone Joint Surg Am 1984 Jul;66(6):817-36. doi: 10.2106/00004623-198466060-00002. PMID: 6376516
Kaitila I, Leisti JT, Rimoin DL
Clin Orthop Relat Res 1976 Jan-Feb;(114):94-106. PMID: 1261139

Clinical prediction guides

Liang H, Hou Y, Pang Q, Jiang Y, Wang O, Li M, Xing X, Zhu H, Xia W
Calcif Tissue Int 2022 Mar;110(3):313-323. Epub 2021 Oct 28 doi: 10.1007/s00223-021-00920-6. PMID: 34709441
Andrzejewski A, Péjin Z, Finidori G, Badina A, Glorion C, Wicart P
J Pediatr Orthop 2021 Feb 1;41(2):e135-e140. doi: 10.1097/BPO.0000000000001708. PMID: 33165262
Briggs MD, Brock J, Ramsden SC, Bell PA
Eur J Hum Genet 2014 Nov;22(11):1278-82. Epub 2014 Mar 5 doi: 10.1038/ejhg.2014.30. PMID: 24595329Free PMC Article
Posey KL, Hecht JT
Curr Drug Targets 2008 Oct;9(10):869-77. doi: 10.2174/138945008785909293. PMID: 18855621
Chen TL, Posey KL, Hecht JT, Vertel BM
J Cell Biochem 2008 Feb 15;103(3):778-87. doi: 10.1002/jcb.21445. PMID: 17570134

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