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
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 defect ...