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Rhizomelic chondrodysplasia punctata type 5(RCDP5)

MedGen UID:
900333
Concept ID:
C4225237
Disease or Syndrome
Synonym: RCDP5
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): PEX5 (12p13.31)
 
Monarch Initiative: MONDO:0014743
OMIM®: 616716
Orphanet: ORPHA468717

Definition

Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life (summary by Wanders and Waterham, 2005). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100. [from OMIM]

Clinical features

From HPO
Clubfoot
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).
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
Swan neck-like deformities of the fingers
MedGen UID:
336516
Concept ID:
C1849152
Finding
A swan neck deformity describes a finger with a hyperextended PIP joint and a flexed DIP joint. The most common cause for a swan neck-like deformity is a disruption of the end of the extensor tendon. Conditions that loosen the PIP joint and allow it to hyperextend, for example conditions that weaken the volar plate, can produce a swan neck deformity of the finger. One example is rheumatoid arthritis. Another cause are conditions that tighten up the small (intrinsic) muscles of the hand and fingers, for example hand trauma or nerve disorders, such as cerebral palsy, Parkinson's disease, or stroke.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Sinus tachycardia
MedGen UID:
11700
Concept ID:
C0039239
Disease or Syndrome
Heart rate of greater than 100 beats per minute.
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.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
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.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Convulsive status epilepticus
MedGen UID:
137148
Concept ID:
C0311335
Disease or Syndrome
A type of status epilepticus characterized by a prolonged bilateral tonic-clonic seizure, or repeated bilateral tonic-clonic seizures without recovery between.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Short femoral neck
MedGen UID:
373033
Concept ID:
C1836184
Finding
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Narrow iliac wing
MedGen UID:
373150
Concept ID:
C1836688
Finding
Decreased width of the wing (or ala) of the ilium (which is the large expanded portion which bounds the greater pelvis laterally).
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.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Thoracic scoliosis
MedGen UID:
387910
Concept ID:
C1857790
Anatomical Abnormality
Contractures of the large joints
MedGen UID:
347211
Concept ID:
C1859698
Finding
Irregular capital femoral epiphysis
MedGen UID:
866530
Concept ID:
C4020825
Anatomical Abnormality
Irregular surface of the normally relatively smooth capital femoral epiphysis.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Developmental cataract
MedGen UID:
3202
Concept ID:
C0009691
Congenital Abnormality
A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.
Horizontal nystagmus
MedGen UID:
124399
Concept ID:
C0271385
Disease or Syndrome
Nystagmus consisting of horizontal to-and-fro eye movements.
Vertical nystagmus
MedGen UID:
75749
Concept ID:
C0271386
Disease or Syndrome
Vertical nystagmus may present with either up-beating or down-beating eye movements or both. When present in the straight-ahead position of gaze it is referred to as upbeat nystagmus or downbeat nystagmus.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRhizomelic chondrodysplasia punctata type 5

Recent clinical studies

Etiology

Morota N, Ihara S, Ogiwara H, Tamura G
J Neurosurg Pediatr 2017 Oct;20(4):378-387. Epub 2017 Aug 11 doi: 10.3171/2017.5.PEDS16554. PMID: 28799855
Duker AL, Niiler T, Eldridge G, Brereton NH, Braverman NE, Bober MB
Am J Med Genet A 2017 Jan;173(1):108-113. Epub 2016 Sep 12 doi: 10.1002/ajmg.a.37961. PMID: 27616591
Argo KM, Toriello HV, Jelsema RD, Zuidema LJ
Ultrasound Obstet Gynecol 1996 Nov;8(5):350-4. doi: 10.1046/j.1469-0705.1996.08050350.x. PMID: 8978012
Wulfsberg EA, Curtis J, Jayne CH
Am J Med Genet 1992 Jul 15;43(5):823-8. doi: 10.1002/ajmg.1320430514. PMID: 1642270
Folz SJ, Trobe JD
Surv Ophthalmol 1991 Mar-Apr;35(5):353-68. doi: 10.1016/0039-6257(91)90185-i. PMID: 1710072

Diagnosis

Muratoğlu Şahin N, Bilici ME, Kurnaz E, Pala Akdoğan M, Ceylaner S, Aycan Z
J Pediatr Endocrinol Metab 2017 Aug 28;30(8):889-892. doi: 10.1515/jpem-2016-0315. PMID: 28742517
Duker AL, Niiler T, Eldridge G, Brereton NH, Braverman NE, Bober MB
Am J Med Genet A 2017 Jan;173(1):108-113. Epub 2016 Sep 12 doi: 10.1002/ajmg.a.37961. PMID: 27616591
Wierzbicki AS, Lloyd MD, Schofield CJ, Feher MD, Gibberd FB
J Neurochem 2002 Mar;80(5):727-35. doi: 10.1046/j.0022-3042.2002.00766.x. PMID: 11948235
Argo KM, Toriello HV, Jelsema RD, Zuidema LJ
Ultrasound Obstet Gynecol 1996 Nov;8(5):350-4. doi: 10.1046/j.1469-0705.1996.08050350.x. PMID: 8978012
Folz SJ, Trobe JD
Surv Ophthalmol 1991 Mar-Apr;35(5):353-68. doi: 10.1016/0039-6257(91)90185-i. PMID: 1710072

Therapy

Dranchak PK, Di Pietro E, Snowden A, Oesch N, Braverman NE, Steinberg SJ, Hacia JG
J Cell Biochem 2011 May;112(5):1250-8. doi: 10.1002/jcb.22979. PMID: 21465523Free PMC Article

Prognosis

Morota N, Ihara S, Ogiwara H, Tamura G
J Neurosurg Pediatr 2017 Oct;20(4):378-387. Epub 2017 Aug 11 doi: 10.3171/2017.5.PEDS16554. PMID: 28799855
Duker AL, Niiler T, Eldridge G, Brereton NH, Braverman NE, Bober MB
Am J Med Genet A 2017 Jan;173(1):108-113. Epub 2016 Sep 12 doi: 10.1002/ajmg.a.37961. PMID: 27616591
Argo KM, Toriello HV, Jelsema RD, Zuidema LJ
Ultrasound Obstet Gynecol 1996 Nov;8(5):350-4. doi: 10.1046/j.1469-0705.1996.08050350.x. PMID: 8978012

Clinical prediction guides

Berger J, Dorninger F, Forss-Petter S, Kunze M
Biochim Biophys Acta 2016 May;1863(5):934-55. Epub 2015 Dec 11 doi: 10.1016/j.bbamcr.2015.12.005. PMID: 26686055Free PMC Article
Buchert R, Tawamie H, Smith C, Uebe S, Innes AM, Al Hallak B, Ekici AB, Sticht H, Schwarze B, Lamont RE, Parboosingh JS, Bernier FP, Abou Jamra R
Am J Hum Genet 2014 Nov 6;95(5):602-10. Epub 2014 Oct 30 doi: 10.1016/j.ajhg.2014.10.003. PMID: 25439727Free PMC Article
Dranchak PK, Di Pietro E, Snowden A, Oesch N, Braverman NE, Steinberg SJ, Hacia JG
J Cell Biochem 2011 May;112(5):1250-8. doi: 10.1002/jcb.22979. PMID: 21465523Free PMC Article
Ofman R, Hettema EH, Hogenhout EM, Caruso U, Muijsers AO, Wanders RJ
Hum Mol Genet 1998 May;7(5):847-53. doi: 10.1093/hmg/7.5.847. PMID: 9536089

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