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Warfarin-induced brachytelephalangic chondrodysplasia punctata

Case presentation

An infant boy weighing 1350 g was born at 29 weeks gestation to a 36-year-old gravid 4, para 2, mother. The mother had multiple medical problems, including a seizure disorder, for which she was being treated with Tegretol, Keppra and Toxamax. During the pregnancy she developed deep venous thrombosis and was placed on Coumadin. She also took Celexa for depression and Lovastatin for hyperlipidemia. After delivery the child had significant respiratory distress, and severe nasal and mid-face hypoplasia was noted. The Apgar scores were 1 at 1 min, 5 at 5 min and 6 at 20 min. Right nostril hypoplasia was present, and a concave facial profile with marked nasal hypoplasia was noted. Physical examination was otherwise normal without cataracts or dermatological findings. A skeletal survey was obtained on the first day of life (Figure 1).

Figure 1

(a) Frontal pelvis. Punctate tiny calcifications in the sacrum, coccyx and greater trochanters (arrows). Umbilical artery and venous catheters in place. (b) Lateral lumbosacral spine: punctate calcifications in the sacrum and coccyx (arrows). (c) Chest radiographs, frontal and lateral: normal without punctuate calcifications in the spine or airway. (d) AP hand radiographs. Strikingly short distal phalanges compared with proximal and middle phalanges.

Denouement and discussion

This child has chondrodysplasia punctata (CP) with small punctate (stippled or paint spattering) calcifications, particularly in the lower spine and pelvis and greater trochanters of the hips. These punctate calcifications may occur in epiphyses, small bones (so-called epiphyseal-equivalent centers) and in the tracheobronchial tree. CP is a radiographic manifestation of a great number of genetic conditions, including autosomal dominant Conradi–Hunermann syndrome, X-linked recessive CP (XRCP), X-linked dominant CP (Happle's syndrome), autosomal recessive rhizomelic CP, Keutel's syndrome and Zellweger's syndrome.1 CP can also occur in non-genetic conditions such as fetal warfarin, diphenylhydantoin and alcohol embryopathies, as well as in maternal autoimmune diseases, especially in system lupus erythematosis.1, 2

In addition to CP, this child has very small distal phalanges in the hands, so-called brachytelephalangy and nasomaxillary hypoplasia. In a male infant, the findings of CP, nasomaxillary dysplasia and brachytelephalangy suggest XRCP or so-called brachytelephalangic CP.3 This diagnosis could be confirmed by demonstration of a defect in the vitamin K-dependent enzyme arylsulfatase E (ARSE), owing to mutations at the Xp chromosome. XRCP is a contiguous gene syndrome to X-linked ichthyosis and to Kallmann's syndrome (anosmia and hypogonadism).4

However, brachytelephalangic CP has been described in infants born to mothers who were treated with warfarin early in pregnancy. Warfarin selectively inhibits ARSE activity.5 Therefore, maternal warfarin produces an identical phenotype to that of XRCP. Our patient did not have defective ARSE, and, given the history, has, therefore, warfarin-induced brachytelephalangic CP.

Patients with fetal warfarin brachytelephalangic CP, or simply warfarin embryopathy, will not have ichthyosis or Kallman's syndrome, however, unlike many patients with XRCP. In addition, warfarin embryopathy can occur with equal frequency in boys and girls.6 The punctate epiphyseal calcifications are only present in infancy, so that later in life the patient may be thought to have a type of epiphyseal dysplasia and associated short stature. However, as in our case, nasomaxillary hypoplasia, referred to as Binder's syndrome, is also a characteristic finding in patients with warfarin-induced brachytelephalangic CP. Binder syndrome can be treated surgically with bone grafting to improve facial appearance and airway function. If the CP involves the tracheobronchial tree, severe tracheal stenosis and respiratory distress can occur, which are sometimes treated by stenting or airway reconstruction.7, 8 If the cervical vertebral bodies are involved, cord compression with poor neurological outcome may occur.9 However, in our case, there are no tracheobronchial calcifications and there is no evidence of involvement of cervical vertebral bodies or of neurological findings. The prognosis of children with warfarin embryopathy is good, with only very minor neurological neurological dysfunction, such as clumsiness, seen in a minority of patients at school age.6 This minor neurological dysfunction is slightly more marked in boys than in girls, but occurs in less than 15% of patients.6 The overall prognosis should be good.


  1. 1

    Bennett CP, Berry AC, Maxwell DJ, Seller MJ . Chondrodysplasia punctata: another possible x-linked recessive case. Am J Med Genet 1992; 44: 795–799.

    CAS  Article  Google Scholar 

  2. 2

    Shanske AL, Bernstein L, Herzog R . Chondrodysplasia punctata and maternal autoimmune disease: a new case and review of the literature. Pediatrics 2007; 102: 436–441.

    Article  Google Scholar 

  3. 3

    Maroteaux P . Brachytelephalangic chondrodysplasia punctata: a possible-x-linked recessive form. Hum Genet 1989; 82: 167–170.

    CAS  Article  Google Scholar 

  4. 4

    Bick D, Curry JR, McGill JR, Schorderet DF, Bux RC, Moore CM . Male infant with ichthyosis, Kallman syndrome, chondrodysplasia punctata and an Xp chromosome deletion. Am J Med Genet 1989; 33: 100–107.

    CAS  Article  Google Scholar 

  5. 5

    Franco B, Meroni G, Parenti G, Levilliers J, Bernard L, Gebbia M et al. A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy. Cell 1995; 81: 15–25.

    CAS  Article  Google Scholar 

  6. 6

    Wesseling J, Vandriel D, Smrkovsky E, vanderVeer E, Geve-Boere LM, Sauer PJJ et al. Neurological outcome in school-age children after in utero exposure to coumarins. Early Hum Dev 2001; 63: 83–95.

    CAS  Article  Google Scholar 

  7. 7

    Kaufmann HJ, Mahoboubi S, Spackman TJ, Capitanio MA, Kirkpatrick J . Tracheal stenosis as a complication of chonrodysplasia punctata. Ann Radiol 1976; 19: 203–209.

    CAS  PubMed  Google Scholar 

  8. 8

    Wolpoe M, Braverman N, Lin SY . Severe tracheobronchial stenosis in the X-linked recessive form of chondrodysplasia punctata. Arch Otolaryngol Head Neck Surg 2004; 130: 1423–1426.

    Article  Google Scholar 

  9. 9

    Herman TE, Lee BCP, McAlister WH . Brachytelephalangic chondrodypslasia punctata with marked cervical cord stenosis and cord compression; report of two cases. Pediatr Radiol 2002; 32: 452–456.

    Article  Google Scholar 

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Correspondence to T E Herman.

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Herman, T., Siegel, M. Warfarin-induced brachytelephalangic chondrodysplasia punctata. J Perinatol 30, 437–438 (2010).

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