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Refers to a heterogeneous group of disorders having in common ichthyosis and bony abnormalities probably as a result of abnormalities of steroidal biosynthesis. The international nomenclature and classification of osteochondrodysplasias categorized the subtypes of chondrodysplasia punctata as (1) rhizomelic type, (2) Zellweger syndrome, (3) Conradi-Hünermann type, (4) X-linked recessive type, (5) brachytelencephalangic type, (6) tibial-metacarpal type, (7) vitamin K-dependent coagulation defect, and (8) other and acquired genetic disorders including warfarin embryopathy. Specific features of the most common individual types of chondrodysplasia punctata are given below.

Toriello-Higgins-Miller Syndrome; Chondrodystrophia Calcificans Congenita: Congenital Stippled Epiphyses.

For rhizomelic chondrodysplasia punctata type I, the incidence in the general population has been estimated to be 1:100,000.

Inherited as a sex-linked recessive trait and caused by a mutation in the arylsulfatase E (ARSE) gene. Known genes are located on Xp22.3 and Xp11.23-p11.22. Other syndromes can be inherited in an autosomal dominant or recessive fashion.

Made clinically based on radiologic signs (calcified stippling of the hyaline cartilage and bones presenting in infancy and disappearing at 2-3 years of age) associated with multiple clinical signs such as limbs with short segments, dysmorphism with a hypoplastic nasal root, skin lesions, and cataracts. Laboratory assays can be used to demonstrate a deficiency in red blood cell plasmalogen, elevated plasma concentration of phytanic acid (although this depends on the food intake), and deficient plasmalogen biosynthesis and phytanic acid oxidation in skin fibroblasts.

This disorder is often associated with prematurity and can be lethal in early infancy. Hypotonia and asymmetry of the body are frequent. Other clinical features can involve the head and neck (brachycephaly, short neck, flat face, frontal bossing, coloboma of the iris, cataract, nystagmus, optic disc anomaly, flattened small nose with anteverted nares, partial absence of the mandible, short columella, long philtrum, tented upper lip, low-set ears with conductive deafness), the limbs (proximal shortening of humeri and femora [rhizomelia], micromelia, epiphyseal anomalies, punctate calcifications of epiphyses, bowed diaphysis, brachydactyly, clinodactyly of the fifth finger, short great toe, small foot, metacarpal anomalies, dislocated hip and restricted joint mobility), the skeleton (flat cheek bones, punctate vertebrae, spina bifida occulta, abnormal vertebral size, pectus excavatum scoliosis), and the skin (absent scalp hair, ichthyosis, cutis marmorata, hypoplastic toenails). Other features that have been described are congenital cardiac lesions, respiratory distress, laryngeal abnormalities, dysplastic kidneys, hydronephrosis and megaureter, abnormal genitalia, splenomegaly, and liver enlargement.

Rhizomelic Chondrodysplasia (RCDP)

Most often, this disorder is inherited in an autosomal recessive and rarely in an X-linked recessive fashion. It is caused by multiple peroxisomal abnormalities. Peroxisomes are ubiquitous cellular organelles involved in different cellular functions, such as β-oxidation of very-long-chain fatty acids (VLCFA), production of plasmalogen (involved in cell membrane integrity) and bile acids, gluconeogenesis, catabolism of purines and polyamines, and ethanol metabolism. The defect can be caused by either abnormally formed peroxisomes associated with several peroxisomal dysfunctions or by a ...

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