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Rhizomelic chondrodysplasia punctata type 1(RCDP1)

MedGen UID:
347072
Concept ID:
C1859133
Disease or Syndrome
Synonyms: Chondrodysplasia punctata rhizomelic form; Chondrodystrophia calcificans punctata; PEROXISOME BIOGENESIS DISORDER 9; RCDP1
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Gene: PEX7
Cytogenetic location: 6q23.3
OMIM: 215100

Disease characteristics

Excerpted from the GeneReview: Rhizomelic Chondrodysplasia Punctata Type 1
Rhizomelic chondrodysplasia punctata type 1 (RCDP1) classic type, a peroxisome biogenesis disorder (PBD), is characterized by proximal shortening of the humerus and to a lesser degree the femur (rhizomelia), punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata, or CDP), coronal clefts of the vertebral bodies, and cataracts that are usually present at birth or appear in the first few months of life. Birth weight, length, and head circumference are often at the lower range of normal; postnatal growth deficiency is profound. Intellectual disability is severe, and the majority of children develop seizures. Most affected children do not survive the first decade of life; a proportion die in the neonatal period. A milder phenotype in which all affected individuals have congenital cataracts and chondrodysplasia is now recognized; some do not have rhizomelia, and some have less severe intellectual disability and growth deficiency. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Nancy E Braverman  |  Ann B Moser  |  Steven J Steinberg   view full author information

Additional descriptions

From OMIM
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. RCDP1 is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Individuals with RCDP1, carrying mutations in the PEX7 gene, have cells of peroxisome biogenesis disorder (PBD) complementation group 11 (CG11, equivalent to CGR). For information on the history of PBD complementation groups, see 214100. Genetic Heterogeneity of Rhizomelic Chondrodysplasia Punctata RCDP2 (222765) is caused by mutation in the gene encoding acyl-CoA:dihydroxyacetonephosphate acyltransferase (GNPAT; 602744) on chromosome 1q42. RCDP3 (600121) is caused by mutation in the gene encoding alkyldihydroxyacetonephosphate synthase (alkyl-DHAP synthase) (AGPS; 603051) on chromosome 2q31. Whereas RCDP1 is a peroxisomal biogenesis disorder (PBD), RCDP2 and RCDP3 are classified as single peroxisome enzyme deficiencies (Waterham and Ebberink, 2012).  http://www.omim.org/entry/215100
From GHR
Rhizomelic chondrodysplasia punctata is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems. Rhizomelic chondrodysplasia punctata is characterized by shortening of the bones in the upper arms and thighs (rhizomelia). Affected individuals also have a specific bone abnormality called chondrodysplasia punctata, which affects the growth of the long bones and can be seen on x-rays. People with rhizomelic chondrodysplasia punctata often develop joint deformities (contractures) that make the joints stiff and painful. Distinctive facial features are also seen with rhizomelic chondrodysplasia punctata. These include a prominent forehead, widely set eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), a small nose with upturned nostrils, and full cheeks. Additionally, almost all affected individuals have clouding of the lenses of the eyes (cataracts). The cataracts are apparent at birth (congenital) or develop in early infancy. Rhizomelic chondrodysplasia punctata is associated with significantly delayed development and severe intellectual disability. Most children with this condition do not achieve developmental milestones such as sitting without support, feeding themselves, or speaking in phrases. Affected infants grow much more slowly than other children their age, and many also have seizures. Recurrent respiratory infections and life-threatening breathing problems are common. Because of their severe health problems, most people with rhizomelic chondrodysplasia punctata survive only into childhood. It is rare for affected children to live past age 10. However, a few individuals with milder features of the condition have lived into early adulthood. Researchers have described three types of rhizomelic chondrodysplasia punctata: type 1 (RCDP1), type 2 (RCDP2), and type 3 (RCDP3). The types have similar features and are distinguished by their genetic cause.  http://ghr.nlm.nih.gov/condition/rhizomelic-chondrodysplasia-punctata

Clinical features

Upslanted palpebral fissure
MedGen UID:
504509
Concept ID:
CN000546
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.
Frontal bossing
MedGen UID:
505049
Concept ID:
CN001816
Finding
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Depressed nasal bridge
MedGen UID:
446656
Concept ID:
CN004681
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of `hearing impairment` (HP:0000365) in one or both ears related to an `abnormal` (PATO:0000460) `functionality` (PATO:0001509) of the `cochlear nerve` (FMA:53431).
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Cerebral cortical atrophy
MedGen UID:
505113
Concept ID:
CN001920
Finding
Atrophy of the cortex of the cerebrum.
Delayed CNS myelination
MedGen UID:
500919
Concept ID:
CN001984
Finding
`Delayed` (PATO:0000502) `myelination` (GO:0042552) in the central nervous system.
Flexion contracture
MedGen UID:
504817
Concept ID:
CN001256
Finding
A flexion contracture is a bent (flexed) joint that 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 of joints.
Frontal bossing
MedGen UID:
505049
Concept ID:
CN001816
Finding
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Kyphoscoliosis
MedGen UID:
425109
Concept ID:
CN002496
Finding
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Flared metaphyses
MedGen UID:
500946
Concept ID:
CN002726
Finding
The presence of splayed (i.e.,flared) metaphyseal segments of the long bones.
Epiphyseal stippling
MedGen UID:
429599
Concept ID:
CN009481
Finding
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses (FMA:24012).
Severe short stature
MedGen UID:
500957
Concept ID:
CN003167
Finding
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
You lose up to 100 hairs from your scalp every day. That's normal, and in most people, those hairs grow back. But many men -- and some women -- lose hair as they grow older. You can also lose your hair if you have certain diseases, such as thyroid problems, diabetes, or lupus. If you take certain medicines or have chemotherapy for cancer, you may also lose your hair. Other causes are stress, a low protein diet, a family history, or poor nutrition. . Treatment for hair loss depends on the cause. In some cases, treating the underlying cause will correct the problem. Other treatments include medicines and hair restoration. .
Ichthyosis
MedGen UID:
429191
Concept ID:
CN007091
Finding
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Flexion contracture
MedGen UID:
504817
Concept ID:
CN001256
Finding
A flexion contracture is a bent (flexed) joint that 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 of joints.
Flexion contracture
MedGen UID:
504817
Concept ID:
CN001256
Finding
A flexion contracture is a bent (flexed) joint that 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 of joints.

Recent clinical studies

Etiology

Ro M, Park J, Nam M, Bang HJ, Yang J, Choi KS, Kim SK, Chung JH, Kwack K
J Child Neurol 2012 Oct;27(10):1270-5. Epub 2012 Feb 28 doi: 10.1177/0883073811435507. [Epub ahead of print] PMID: 22378669

Diagnosis

Oswald G, Lawson C, Raymond G, Golden WC, Braverman N
Am J Med Genet A 2011 Dec;155A(12):3160-3. Epub 2011 Nov 3 doi: 10.1002/ajmg.a.34331. [Epub ahead of print] PMID: 22052861
Başbuğ M, Serin IS, Ozçelik B, Guneş T, Akçakuş M, Tayyar M
Fetal Diagn Ther 2005 May-Jun;20(3):171-4. doi: 10.1159/000083899. PMID: 15824492
van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJ
Am J Hum Genet 2003 Feb;72(2):471-7. Epub 2003 Jan 9 [Epub ahead of print] PMID: 12522768Free PMC Article
Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJ, Waterham HR
Am J Hum Genet 2002 Mar;70(3):612-24. Epub 2002 Jan 7 doi: 10.1086/338998. [Epub ahead of print] PMID: 11781871Free PMC Article

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

Oswald G, Lawson C, Raymond G, Golden WC, Braverman N
Am J Med Genet A 2011 Dec;155A(12):3160-3. Epub 2011 Nov 3 doi: 10.1002/ajmg.a.34331. [Epub ahead of print] PMID: 22052861
Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJ, Waterham HR
Am J Hum Genet 2002 Mar;70(3):612-24. Epub 2002 Jan 7 doi: 10.1086/338998. [Epub ahead of print] PMID: 11781871Free PMC Article

Clinical prediction guides

Wood PL, Khan MA, Smith T, Ehrmantraut G, Jin W, Cui W, Braverman NE, Goodenowe DB
Lipids Health Dis 2011 Oct 18;10:182. doi: 10.1186/1476-511X-10-182. [Epub ahead of print] PMID: 22008564Free 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
Motley AM, Brites P, Gerez L, Hogenhout E, Haasjes J, Benne R, Tabak HF, Wanders RJ, Waterham HR
Am J Hum Genet 2002 Mar;70(3):612-24. Epub 2002 Jan 7 doi: 10.1086/338998. [Epub ahead of print] PMID: 11781871Free PMC Article

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