Chondrodysplasia punctata is a term encompassing a group of inherited skeletal dysplasias characterized by calcified deposits on the epiphyseal parts of the bone and cartilage, and they are termed stippling. The clinical presentation somewhat depends on the subtype, but commonly involves shortening of the extremities, facial changes, spinal deformities, ocular abnormalities, developmental delay and congenital heart disease. The diagnosis rests on a thorough clinical workup, imaging studies, and genetic testing.
Chondrodysplasia punctata (CDP) is a term that comprises several congenital disorders with different modes of inheritance. They are rarely encountered in clinical practice and the two principal types are   :
- Brachytelephalangic chondrodysplasia punctata - Considered as a benign form of CDP, Brachytelephalangic CDP occurs due to arylsulfatase E (ARSE) gene mutations that are transferred through X-linked recessive patterns    . As a result, this type is seen almost exclusively in boys . The distal phalanges of the feet and hands exhibit significant shortening (brachytelephalangy), whereas hypoplasia of the midface and the nasal bones are notable facial features   . Patients suffering from this type of CDP do not develop dwarfism or ocular abnormalities, which is typical for more severe forms of CDP - Rhizomelic CDP .
- Rhizomelic chondrodysplasia punctata (RCDP) - Arising due to disruption of normal synthesis of peroxisomes (vital cell membrane constituents) through PEX7 gene mutations, this autosomal recessive type of CDP is distinguished by the presence of early-onset mental retardation and a short stature that predominantly involves the humerus and the femur (termed rhizomelia)     . Facial dysmorphism is more pronounced than in brachytelephalangic CDP, whereas congenital heart disease (seen in up to 50% of patients), cataracts, recurrent respiratory infections, seizures and an overall shorter life span are additional features     . Spinal deformities, such as scoliosis, are seen across all forms of CDP .
Entire Body System
Failure to Thrive
Abstract Rhizomelic chondrodysplasia punctata is a rare genetic disorder of peroxisomal metabolism that is characterized clinically by shortening of the proximal limbs, cataracts, a characteristic facial appearance, failure to thrive, and psychomotor [ncbi.nlm.nih.gov]
[…] sepsis • Weight at death 2.5 kg (Failure to thrive) 6. Second Child • Antenatal history - ? Polyhydramnios • Term born/3.5kgs/Respiratory distress at birth Nicu stay x 20 days. [slideshare.net]
All affected infants have severe failure to thrive, mental retardation, joint contractures, and cataracts. [mhmedical.com]
A 5-year-old girl presented for evaluation of ill-defined patches of cicatricial alopecia. In addition, subtle follicular atrophoderma, esotropia, craniofacial asymmetry and short stature were noted. [ncbi.nlm.nih.gov]
· Cutaneus abnormalities: ichthyosis and hyperkeratosis; alopecia; layered and split nails. Prognosis - Chondrodysplasia punctata Not supplied. Treatment - Chondrodysplasia punctata Not supplied. Resources - Chondrodysplasia punctata Not supplied. [checkorphan.org]
Ectodermal changes include alopecia, cataract, ichthyosis and hyperkeratosis. [ijri.org]
He presented with aggressive and hyperactive behavior. [ncbi.nlm.nih.gov]
Patients most frequently present with hyperreflexia (21%) and weakness (21%), and there were various conservative treatment strategies. [ncbi.nlm.nih.gov]
Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. [ncbi.nlm.nih.gov]
The rare occurrence of CDP in general practice (< 1 in 100,000 patients) indicates that the condition may be difficult to diagnose without a thorough workup . For this reason, physicians must perform a complete neurological, cardiorespiratory, and mental examination, preceded by a patient history that will evaluate the potential presence of similar disorders within the family . After the initial assessment, imaging studies should be performed. Ultrasonography and plain radiography are two very useful first-line methods that are able to confirm the presence of epiphyseal stippling and punctate calcifications, as well as hypoplasia of facial bones and the distal extremities  . Ultrasonography provides an additional benefit in that, it has the ability to detect changes prenatally , thus providing sufficient time to plan adequate therapeutic strategies. Moreover, cardiac ultrasonography (both prenatally and postnatally) has been recommended as a mandatory imaging study in CDP patients due to the high rate of congenital heart disease . A comprehensive neurological testing, particularly in the presence of epilepsy (through electroencephalography, evoked potentials, and other similar studies), is also warranted . Finally, genetic testing of both the parents and the patient should be conducted  .
- Benaicha A, Dommergues M, Jouannic JM, et al. Prenatal diagnosis of brachytelephalangic chondrodysplasia punctata: case report. Ultrasound Obstet Gynecol. 2009;34(6):724-726.
- Gupta N, Ghosh M, Shukla R, Das GP, Kabra M. Brachytelephalangic chondrodysplasia punctata: a case series to further delineate the phenotype. Clin Dysmorphol. 2012 Jul;21(3):113-117.
- Huffnagel IC, Clur SA, Bams-Mengerink AM, et al. Rhizomelic chondrodysplasia punctata and cardiac pathology. J Med Genet. 2013;50(7):419-424.
- Casarin A, Rusalen F, Doimo M, et al. X-linked brachytelephalangic chondrodysplasia punctata: a simple trait that is not so simple. Am J Med Genet A. 2009;149A(11):2464-2468.
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- Çim A, Coşkun S, Görükmez O, et al. Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene. J Clin Res Pediatr Endocrinol. 2015;7(1):69-72.
- Tinnion RJ, Davidson N, Moran P, Wright M, Harigopal S. Rhizomelic chondrodysplasia punctata: a classic “spot” diagnosis. BMJ Case Rep. 2011;2011:bcr0120113747.
- Mason DE, Sanders JO, MacKenzie WG, Nakata Y, Winter R. Spinal deformity in chondrodysplasia punctata. Spine (Phila Pa 1976). 2002;15;27(18):1995-2002.