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Punctate calcification of the epiphyses, visceral malformations, and craniofacial dysmorphism in a female baby
  1. ANNE SLAVOTINEK,
  2. HELEN KINGSTON
  1. University Department of Medical Genetics and Regional Genetic Service, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK
  1. Dr Kingston,helenk{at}central.cmht.nwest.nhs.uk

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Editor—We report a fetus with striking craniofacial dysmorphism, brachydactyly, and cerebral and cardiac malformations in addition to punctate calcification of the epiphyses.

The mother was treated for tuberculosis seven years before the pregnancy but there were no known systemic illnesses or teratogenic influences during this pregnancy. The mother's first pregnancy resulted in a termination at 22 weeks of gestation for multiple congenital abnormalities, but further details are not known.

The baby was the second child born to a 21 year old mother. A termination was performed at 21 weeks of gestation because of multiple anomalies seen on antenatal scanning. Necropsy showed a female fetus (fig 1) with a weight of 1544 g, consistent with 17 weeks' gestation. The crown-heel length was 16.4 cm and right foot length was 18 mm. Facial examination showed an open right eye with exophthalmos, hypertelorism, a flat nasal bridge with hypoplasia of the alae nasi, flattening of the midface, a short philtrum with a well defined philtral groove, large lips, and a wide mouth with micrognathia. The right ear was simple and low set and the left ear was rudimentary and poorly formed. The palate was normal. Both hands had brachydactyly involving all digits with short thumbs. There were bilateral varus foot deformities and both feet were rockerbottom in shape. The remainder of the examination showed nuchal thickening, a short, broad chest, and a straight spine. The genitalia were female with a vaginal opening but there was clitoral hypertrophy and prominence of the labial folds.

Figure 1

(A) Front view of fetus. (B) Hand of fetus. (C) Foot of fetus.

Internal examination of the brain showed enlargement of both lateral cerebral ventricles, absent olfactory bulbs, and an absent pituitary gland. The heart had a common truncus arising from the right ventricle with a high ventricular septal defect. The right adrenal gland was absent. Histological sections showed that one umbilical artery was rudimentary without a lumen. Examination of the placenta showed no inflammatory changes. Unfortunately, no histological studies were performed on bone.

Chromosome analysis showed an apparently normal female karyotype but the quality of the preparation was sufficient only to exclude numerical and large structural abnormalities. Culture of the fetal cells failed and peroxisomal studies and a 7-dehydrocholesterol level were not performed.

Radiographs (fig 2) showed extensive calcification and stippling in all epiphyseal areas. There was undermodelling of the long bones with shortening of the humeri and relative widening of the diaphyses. There was poor calcification and sagittal clefting of the vertebral bodies. Radiographs of the hands and feet showed stippling in the carpal and tarsal bones and the fingers and toes were extremely short with a single phalanx in the second to fifth digits and almost absent ossification of the phalanges. The thorax was short and broad with 11 pairs of ribs and there was posterior dislocation of the hips. The couple chose not to attend genetic counselling clinic.

Figure 2

Radiograph of fetus showing punctate calcification of epiphyseal areas and stippling of carpal and tarsal bones.

This baby had an unusual pattern of malformations including right exophthalmos, midface hypoplasia, rudimentary ears, cerebral ventriculomegaly, a common truncus arteriosus and ventricular septal defect, and extreme brachydactyly in addition to calcific stippling of the epiphyses. Epiphyseal stippling can be found in the primary chondrodysplasias,1 but the visceral abnormalities in this baby are not typical of chondrodysplasia and the presentation is neither consistent with brachytelephalangic chondrodysplasia punctata (CP)2 3 or humerometacarpal CP.4 5 One plausible diagnosis is Pacman dysplasia, a rare condition in which stippling of the lower spine and epiphyses has been found with bowing of the femora, spinal clefting, and giant, multinucleated, osteoclast-like cells.6 7 Although a patent ductus was described in one child, Pacman dysplasia has not been reported with severe visceral abnormalities or craniofacial dysmorphism as found in this baby.

Stippling of the epiphyses is well known to be causally heterogeneous,1 8 but syndromes with punctate calcification and visceral malformations are rare. Two sibs were described with short stature, ocular colobomata, midface hypoplasia with a small nose, low set ears, and dysplastic distal phalanges in addition to stippled epiphyses.9 A second report of a girl with similar facial dysmorphism, a right retinal coloboma and an incomplete atrioventricular canal, coarctation of the aorta, enlargement of the anterior horns of the lateral ventricles, and partial agenesis of the corpus callosum concluded that these anomalies comprised a separate syndrome.10 Recently, a male baby with punctate epiphyses and coronal clefting of the spine was described with a Dandy-Walker malformation, hypogenesis of the corpus callosum and falx cerebri, a ventricular septal defect, and bilateral cleft lip and palate.11 This child also had craniofacial dysmorphism with telecanthus, clouding of the corneas, a high nasal bridge and retromicrognathia, and brachydactyly.

These cases show a degree of similarity to this baby with calcific stippling in association with midface and nasal hypoplasia, dysplastic ears, brachydactyly, and cranial and cerebral malformations. However, the variable nature of the accompanying anomalies makes it difficult to be confident that these patients represent heterogeneity of the same condition. Despite the incomplete clinical information in our case, we believe that documentation of these abnormalities will prove useful in view of the rarity of the combination of features and the paucity of reports describing epiphyseal stippling and malformations.

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