118 Short case report

Chondrodysplasia punctata tibia metacarpal type: report of a 1.5 year old child with severe short stature and extensive calcific stippling Anju Shukla and Shubha R. Phadke Clinical Dysmorphology 2015, 24:118–121 Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Tel: + 91 522 2494325; fax: + 91 522 2668017; e-mail: [email protected] Received 3 February 2014 Accepted 16 December 2014

Correspondence to Shubha R. Phadke, MD (Paediatrics), DM (Medical Genetics), Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India

List of key features Midface retrusion Depressed nasal bridge Short neck Micromelia Short fingers

Introduction The latest nosology and classification of genetic skeletal disorders describe at least 10 types of chondrodysplasia punctata (CDP) (Warman et al., 2010). This group has been classified on the basis of abnormal mineralization and is characterized by the presence of stippling in certain parts of the skeletal system seen during infancy, which disappears at later age. CDP tibia metacarpal (CDP-TM) type is a very rare variety of CDP, characterized by variable long-bone shortening with the fibula longer than the tibia, short metacarpals especially the fourth, and variable shortening of the proximal and distal phalanges. We describe a 1 year 6 months old child with severe short stature, extensive calcific stippling, and severe shortening of metatarsals, which have not been described earlier. The etiology, inheritance, and molecular basis of this disorder still need to be characterized.

(50th centile). The neck was short with the presence of micromelia, especially rhizomelia (Fig. 1a). He had midface retrusion with a depressed nasal bridge (Fig. 1b). The second digits of both the upper and the lower limbs were short and proximally placed (Fig. 1c). The hand showed a trident configuration (Fig 1d). The chest was symmetrical with mild pectus carinatum. There was no ichthyosis, spinal deformity, hypotonia, contractures, cleft palate, cardiac defects, nor any genital abnormalities. Skeletal survey of the spine revealed the presence of rounded vertebral bodies with decreased height (Fig. 2a). There was a presence of punctate calcification in the sacral area. The iliac bones were axe shaped (Fig. 2b). Imaging of the long bones of the upper limbs showed a short humerus and distal ulnar hypoplasia. Stippling was also seen in the carpal, metacarpals, and the phalanges. The first, fourth, and fifth metacarpals, all the distal phalanges of the hand, and the proximal phalanx of the second digit were very short (Fig. 2c). The femur was short and bent with widened metaphyses. The fibula was longer, overshooting the tibia at the upper end (Fig. 2d). There was severe shortening of the first, second, and third metatarsals as well as the phalanges in both feet (Fig. 2e). Lateral radiography of the skull and face showed maxillary hypoplasia with concavity of the infraorbital region.

Case report A 1 year 6 months old child was brought to the Medical Genetics Outpatient Department with complaints of short stature, especially short limbs and relatively large head, which were noticed at birth by the parents. The child was born at term, single, by normal vaginal delivery with no other significant perinatal history. There was no history of drug intake, rashes, nor joint pain in the mother during the antenatal period. The child did not have any history of recurrent fractures nor recurrent lower respiratory tract infections. He had a vocabulary of 8–10 words, understood simple commands, and could walk with support at 18 months. He was a product of a nonconsanguineous marriage. There was no history of similar nor related illness in the family, and the parents have normal stature. On examination, his length was 63 cm (− 7 SD as per Indian standards) and head circumference was 45 cm

Discussion CDP-TM type is a very rare genetic skeletal disorder. This subtype of CDP was first reported as early as 1951 (Haynes and Wangner, 1951), but was described as a discrete entity, TM type by Burck (1982), and hence it is also referred to as CDP, Burck type. It occurs as a sporadic disorder, and both men and women are equally affected suggestive of a probable autosomal dominant mode of inheritance (Rittler et al., 1990). There has been a single report of two affected siblings (Honda et al., 2008) in the literature to date suggesting either a possibility of recessive mode of inheritance or gonadal mosaicism. The present case in addition to stippled calcification has characteristic facial features and short metacarpals and tibia consistent with the diagnosis of CDP-TM.

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DOI: 10.1097/MCD.0000000000000076

CDP-TM type: report of a 1.5 year old child Shukla and Phadke 119

Fig. 1

(a) Short limb short stature with rhizomelia and short neck. (b) Severe midface retrusion. (c) Proximally placed second toe. (d) Trident hand.

The other genetic and nongenetic causes of CDP, such as rhizomelic CDP, X-linked varieties of CDP, CHILD syndrome, Greenberg dysplasia, spondyloepimetaphyseal dysplasia (short limb-abnormal calcification type) and spondylomegaepiphyseal dysplasia with upper limb mesomelia, punctate calcifications and deafness, warfarin embryopathy, Smith–Lemeli–Opitz syndrome, Zellweger syndrome, trisomy 18, trisomy 21, fetal alcohol syndrome, congenital rubella syndrome, etc., are unlikely in our case.

is disproportionate short stature with short neck and short limbs. Patients may display rhizomelia, mesomelia, or micromelia. Their height is usually 2–4 SDs below the median, and their psychomotor development is normal. There is presence of short tibiae, short fourth metacarpals, very short proximal phalanx of the second digit, and vertebral abnormalities that include coronal clefts and deficient ossification. There is stippled calcification involving the sacral, tarsal, and carpal regions which is most marked in the newborn period.

The initial description of seven cases by Rittler et al. (1990), including two cases of Burck (1982) provided the comprehensive clinical and radiographic features of this variety of CDP. These authors also reviewed and included in their description previously reported cases. The natural history of the disease has been elucidated by Savarirayan et al. (2004) in three patients, who were followed up to middle age. All three had normal physical and mental development. Few complications related to auditory function, lumbar canal stenosis, hip dysplasia, and recurrent patellar dislocation were seen, which were appropriately managed.

The present child’s radiographs at the age of 6 months and 1 year 4 months are available, which show extensive punctate calcification especially in the metacarpals. Among the previously reported cases of CDP-TM that were less than 2 years, such extensive changes have not been reported to date. This case may represent the severe end of this disorder due to the extensive calcification, severe short stature, and very short bones of the digits. The child had trident hand secondary to these short bones of the hands.

CDP-TM is distinguished by features of hypoplastic midface, depressed nasal bridge, small mouth, and micrognathia. There

Prenatal diagnosis of rhizomelic CDP has been reported (Argo et al., 1996) by antenatal ultrasound, but the diagnosis of type of CDP could be confirmed only postnatally. However, a single case of CDP-TM has been diagnosed

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120 Clinical Dysmorphology

2015, Vol 24 No 3

Fig. 2

(a) Severe platyspondyly, ovoid vertebrae, and punctate calcification in sacral area. (b) Radiographic pelvis showing axe-shaped iliac bones. (c) Radiographs of the hand at 6 months and at 1.5 years – note disappearing punctate lesions. (d) Short tibia and overshooting fibula. (e) Severe shortening of the metatarsals and phalanges in the feet.

prenatally using multidetector computed tomography with three dimensional computed tomographic reconstructions (Miyazaki et al., 2007), which could definitely help in appropriate genetic counseling for the family because of the heterogenous etiology of CDP. Rarely, this disorder has also been found in a fetus with phenytoin exposure during pregnancy. It has not been reported in

cases with other teratogens nor has it been found associated with maternal systemic lupus erythematosus. The clinical and radiographic details of our case reflect more severe involvement resulting in severe stippling, trident hand, and proximal placement of the second digits. These phenotypic differences can be attributed

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CDP-TM type: report of a 1.5 year old child Shukla and Phadke 121

to the severe shortening of the metacarpal bones. Moreover, the short and broad first and second metatarsal bones have not been reported in any of the previous cases of this disorder. Conclusion

This case illustrates a case of CDP-TM with extensive stippling and extremely short digital bones showing the more severe end of this disorder.

Acknowledgements The authors thank Indian Council of Medical Research for funding the project. They also thank the patient and his family for their cooperation and support. Conflicts of interest

There are no conflicts of interest.

References Argo KM, Toriello HV, Jelsema RD, Zuidema LJ (1996). Prenatal findings in chondrodysplasia punctata, tibia-metacarpal type. Ultrasound Obstet Gynecol 8:350–354. Burck U (1982). Mesomelic dysplasia with punctate epiphyseal calcifications – a new entity of chondrodysplasia punctata? Eur J Pediatr 138:67–72. Haynes ER, Wangner WF (1951). Chondroangiopathia calcarea seu punctata; review and case report. Radiology 57:547–550. Honda R, Ichiyama T, Maeba S, Sunagawa S, Furukawa S (2008). Male siblings with tibia-metacarpal type of chondrodysplasia punctata without maternal factors. Brain Dev 30:301–304. Miyazaki O, Nishimura G, Sago H, Watanabe N, Ebina S (2007). Prenatal diagnosis of chondrodysplasia punctate tibia–metacarpal type using multidetector CT and three-dimensional reconstruction. Pediatr Radiol 37:1151–1154. Rittler M, Menger H, Spranger J (1990). Chondrodysplasia punctata, tibia-metacarpal (MT) type. Am J Med Genet 37:200–208. Savarirayan R, Boyle RJ, Masel J, Rogers JG, Sheffield LJ (2004). Longterm follow-up in chondrodysplasia punctata, tibia-metacarpal type, demonstrating natural history. Am J Med Genet A 124A:148–157. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, et al. (2011). Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A:943–968.

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Chondrodysplasia punctata tibia metacarpal type: report of a 1.5 year old child with severe short stature and extensive calcific stippling.

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