(Conradi-Hünermann syndrome, Conradi-Hünermann-Happke syndrome, Conradi syndrome, congenital calcificans chondrodysplasia, Happle syndrome, calcinosis universalis, punctata epiphyseal disease)Presence of erratic calcifications in cartilage, that disappear around the age of 2-3 years. This anomaly can be found in various syndromes but this appellation is reserved to a heterogeneous group of peroxisomal disorders causing, among others, an anomaly of the synthesis of steroids and hypocholesterolemia.
Different subtypes have been individualised:
- rhizomelic type chondrodysplasia punctata (Conradi syndrome) [MIM 215 100], autosomal recessive transmission of a mutation of PEX7 gene (6q23.3) (type 1) or a mutation of GNPAT gene (1q42) (dihydroxy-acetone phosphate acyltransferase) (type 2) [MIM 222 765] or of AGPS gene (2q31) (alkyl-DHAP synthase) (type 3) or of PEX5 (12p13.31) (deficit of the alpha oxidation of phytanic acid) (type 5) [MIM 616 716]; short stature; microcephaly, flat facies, hypertelorism, arched or cleft palate; symmetric shortening of the limbs, with contractures of the joints; skin lesions: ichthyosis and localized hyperkeratosis; cataract, severe mental retardation and disorders of myelination. Death before 2 years of age in the majority of cases.
- brachytelephalangic type chondrodysplasia punctata [MIM 302 950; 602 497] X-linked dominant transmission, (CDPX1) of a mutation in ARSE gene (Xp) gene that causes a deficiency in arylsulfatase E in the system of Golgi; in addition to the chondrodysplasia punctata, there is an nasomaxillar hypoplasia, and a brachytelephalangia (short terminal phalanges); although most patients live quite normally, some have respiratory disorders related to nasal hypoplasia or tracheobronchial calcifications ; some patients present with a cervical vertebral canal stenosis and/or instability of the cervical vertebrae; sometimes: heart defects (ASD, VSD, patent ductus arteriosus), eye defects (cataracts, small optic nerves).
- X-linked chondrodysplasia punctata (dominant transmission) [MIM 302 960] (Conradi-Hünermann-Happke or CDPX2), generally lethal for male children, due to a mutation of gene EBP (Xp11.23 - p11.22) coding for the 3β-Hydroxysteroid-δ (8), δ(7) - isomerase) which is involved in the synthesis of cholesterol: small, asymmetric shortening of limbs, dislocation of hip, scoliosis; skin lesions (95%): striated hyperkeratosis, areas of alopecia; sometimes baby collodion or non-bullous ichthyoid erythroderma following the Blashko lines at birth but improvement and even or disappearance of the ichthyosis with time ; eye anomalies (2/3): microphthalmia, microcornea, cataract, glaucoma; facial dysmorphism: bossing of the forehead, hypertelorism, low nasal curvature, malar hypoplasia, alopecia on scar areas.
- X-linked chondrodysplasia punctata (recessive transmission) [MIM 302 950] reported only in a few boys
- tibio-metacarpal chondrodysplasia punctata (autosomal dominant transmission)
- type Toriello chondrodysplasia punctata : rare, probably autosomal recessive transmission: short stature, facial dysmorphism, coloboma, affecting the proximal epiphysis of the humerus
- Zellweger syndrome (see this term)
In addition to these inherited forms, there are also the so-called acquired (and often less severe) forms of chondrodysplasia punctata associated with the warfarin-linked embryopathy, the hydantoin-linked embryopathy, maternal alcohol consumption, congenital deficiency in vitamins or maternal disseminated lupus erythematosus.
according to the form,
- risk of difficult intubation and of subglottic stenosis by laryngeal or tracheal calcification
- instability of the cervical spine
- cardiac malformation
- in case of ichthyosis, difficulties with venous access and/or securing catheters and tubes
- scoliosis, short stature
- mental retardation.
Updated: May 2021