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At a glance

Refers to a heterogeneous group of disorders having in common ichthyosis and bony abnormalities, most likely 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) brachytelephalangic 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.

Synonyms

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

Incidence

For rhizomelic chondrodysplasia punctata Type I, the estimated incidence in the general population is in the range of 1:100,000.

Genetic inheritance

Inherited as a sex-linked recessive trait and caused by mutations 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.

Diagnosis

Made clinically based on the radiologic signs (calcified stippling of the hyaline cartilage and bones, presenting in infancy and disappearing by 2-3 years of age) associated with multiple clinical features such as limbs with short segments, facial dysmorphism with 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 nutrition), and deficient plasmalogen biosynthesis and phytanic acid oxidation in skin fibroblasts.

Clinical aspects

This disorder is often associated with prematurity and can be lethal in early infancy. Hypotonia and asymmetry of the body are frequent. Head and neck anomalies my include brachycephaly, frontal bossing, flat face with flat cheek bones, low-set ears with conductive deafness, 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, and short neck. Limbs anomalies may consist of 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. Skeletal anomalies may include spina bifida occulta, abnormal vertebral size, punctate vertebrae, scoliosis, and pectus excavatum. Skin changes may include absent scalp hair, ichthyosis, cutis marmorata, and hypoplastic toenails. Other features that have been described are congenital cardiac lesions, respiratory distress, laryngeal abnormalities, renal dysplasia, hydronephrosis and megaureter, abnormal genitalia, splenomegaly, and liver enlargement.

  • Rhizomelic Chondrodysplasia (RCDP; Rhizomelic Chondrodysplasia Punctata Type 1): 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 ...

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