Synonyms: Conradi‑Hünermann syndrome, Chondrodystrophia calcificans congenita.
Prevalence: Over 100 reported cases, many in Australia.
Definition: Depressed nasal bridge, mild stippling of the epiphysis (premature calcifications in ultrasound) that affects the vertebrae, tarsal and carpal bones.
Etiology: Autosomal dominant.
Pathogenesis: Disruption of the physis with abnormal calcification.
Associated Anomalies: Postaxial polydactyly (occasional).
Differential Diagnosis of abnormal coccygeal and talar calcifications: warfarin embryopathy, aneuploidy (trisomies 18, 21, triploidy), anencephaly, alcohol and phenytoin exposure, peroxisomal disorders, Smith‑Lemli‑Opitz syndrome, GM1 gangliosidosis.
Related anomalies: Chondrodysplasia punctata (X‑linked dominant type), Dysplasia epiphysealis punctata, Rhizomelic chondrodysplasia punctata.
Prognosis: Bone changes improve in the mild form; the lifespan and intelligence are normal. The only marker in adults is the nasal anomaly.
Risk of recurrence: Mendelian inheritance.
Management: Standard prenatal care.
MESH Chondrodysplasia‑Punctata ‑pathology; ‑diagnosis; ‑genetics; Femur‑abnormalities; Humerus‑abnormalities BDE 0153 MIM 11865 POS 3065 ICD9 756.59 CDC 756.575
* Address correspondence to Margaret E. Furness, FRACR, DDU, The Queen Victoria Hospital, 160 Fullarton Road, Rose Park, South Australia 5067, Phone 61‑8‑333 9105 Fax 61‑8‑333 9184
Chondrodysplasia punctata refers to a heterogeneous group of conditions which share calcific stippling of cartilage and periarticular soft tissues and, in particular, punctate calcification in the heel, in infancy. These disorders differ in clinical features, severity, inheritance pattern and radiological features, and an agreed upon classification has yet to be established.
The rhizomelic type1 (an autosomal recessive disorder of peroxisomal function) is usually lethal in infancy and consists of proximal limb shortening, short stature, flat facies, cataracts, mental retardation and ichthyosiform skin rash.
The X‑linked dominant type2, thought to be lethal in males, is characterized by asymmetrical skeletal abnormalities with short stature, shortening of the long bones, dysplasia and contracture of joints, and scoliosis together with flat nasal bridge, congenital ichthyosiform erythroderma, cicatricial alopecia of the scalp, abnormal hair and cataracts.
An X‑linked recessive form has been described3 in association with a deletion of the terminal short arm of an X chromosome, in brothers with epiphyseal stippling, nasal hypoplasia, ichthyosis and mental retardation.
The term Conradi‑Hünermann syndrome has been applied to an apparently heterogeneous group of conditions whose features include asymmetrical short stature, scoliosis, cataracts, ichthyotic skin and flat facies with nasal hypoplasia4. The patients included some with X‑linked dominant, autosomal dominant5 and sporadic forms6, and can be quite mildly affected. Patients with the mildest clinical features have been diagnosed in mid‑childhood to have Binder syndrome (maxillo‑nasal dysplasia)7.
Other causes of calcific epiphyseal stippling include warfarin8, alcohol, and phenytoin exposure in pregnancy, several peroxisomal disorders including Zellweger1 syndrome, Smith‑Lemli‑Opitz9 syndrome, trisomies 18 and 2110, GM1 gangliosidosis11 and anencephaly.
Chondrodysplasia punctata has been diagnosed by third‑trimester ultrasound in an at‑risk fetus12, and an association with fetal ascites and polyhydramnios has been reported13.
Radiographically visible ossification begins in the calcaneum and talus between 22 and 24 weeks of menstrual age10. Ossification in the first coccygeal segment usually begins after term, but may occasionally be seen in mid‑third trimester.
The first pregnancy of a non‑consanguineous couple ended in unexplained fetal death of a male at 31 weeks" gestation. At the time of the second pregnancy, the mother was 28 years old and measured 1.53 m; she had been on no medication. The father was 31, and 1.70 m tall. Neither had the facies of chondrodysplasia punctata.
Ultrasound scan of the second pregnancy at 15 weeks" gestation showed striking echogenicity of the coccyx (fig. 1).