Familial Patent Ductus Arteriosus: A Further Case ofCHAR Syndrome

Anne Slavotinek,1,2* Jill Clayton-Smith,1 and Maurice Super2

1Department of Clinical Genetics, St. Mary’s Hospital, Manchester, United Kingdom2Department of Clinical Genetics, Royal Manchester Childrens Hospital, Manchester, United Kingdom

We report on a family with patent ductusarteriosus, a distinctive facial appearancewith eyebrow flare, a short nose and ‘‘duck-bill lips,’’ polydactyly, and fifth finger clino-dactyly. The facial traits were consistentwith CHAR syndrome. We provide furtherevidence for evolution of the phenotypewith age and describe the previously unre-ported finding of interstitial polydactyly inthis syndrome. Am. J. Med. Genet. 71:229–232, 1997. © 1997 Wiley-Liss, Inc.

KEY WORDS: CHAR syndrome; familialpatent ductus arteriosus; au-tosomal dominant

INTRODUCTION

Familial patent ductus arteriosus was previously re-ported in association with a distinctive facial appear-ance in CHAR syndrome [Char, 1978; Temple, 1992;Sletten and Pierpont, 1995] and in one other family[Davidson, 1992]. CHAR syndrome is an autosomaldominant condition comprising ptosis, low-set ears,short philtrum and ‘‘duck-bill’’ lips, patent ductus ar-teriosus, a single fifth finger flexion crease with twofifth finger phalanges, and mild learning difficulties[Temple, 1992]. A broad forehead, flared eyebrows,mild hypertelorism, flat midface, and strabismus havealso been described in affected individuals [Char, 1978;Temple, 1992].

We report on a family with patent ductus arteriosus,a distinctive facial appearance, interstitial polydactyly,and fifth finger clinodactyly. The facial findings of flar-ing eyebrows, a short, flat nose, and a short philtrumwith duck-bill lips in the younger relatives were con-sistent with CHAR syndrome. The mode of inheritanceis autosomal dominant, with incomplete penetrance ofthe patent ductus arteriosus. We think that careful at-tention should be given to the facial traits of children

with patent ductus arteriosus before the estimation ofrecurrence risks.

CLINICAL REPORT

The pedigree is shown in Figure 1. The propositus(III-3) was the third child born to healthy, unrelatedCaucasian parents. Both parents were 28 years old atthe time of birth. He was born at term by normal vagi-nal delivery with a weight of 2,950 g (3rd to 10th cen-tile). A short nose was noted at birth. At 5 months, apatent ductus arteriosus was diagnosed after investi-gations for repeated upper respiratory tract infections.Surgical repair was performed successfully by deviceocclusion at 2 years.

On examination at 27⁄12 years (Fig. 2), his length was84.5 cm (3rd to 10th centile) and head circumferencewas 47.5 cm (3rd to 10th centile). He had a flat occiputand a flat facial profile. The eyes and ears were normal,but the nose was short and broad with a flat nasalbridge and nasal tip. He had a short philtrum andthick, fleshy lips with a wide mouth. Examination ofthe hands showed fifth finger clinodactyly with normalflexion creases. There were two small cafe-au-laitpatches on his trunk and on his leg. The genitalia werenormal.

The propositus’ sister (III-1) was born normally at 36weeks of gestation with a weight of 2,650 g (50th to75th centile). Neonatally she was treated with a splintfor dislocation of the left hip. At 2 years, a patent duc-tus arteriosus was diagnosed. Surgical ligation of alarge ductus arteriosus (diameter 4–6 mm) was per-formed at 4 years because of recurrent fatigue.

At age 311⁄12 years, her height was 93 cm (3rd to 10thcentile) and her weight was 12.65 kg (<3rd centile). Shehad interstitial polydactyly of her left foot, with com-plete syndactyly of the left fifth and sixth toes, andpartial syndactyly of the fourth and fifth toes (Fig. 3).The accessory left fifth toe was surgically removed atthe age of 6 years. Her hands were normal. She had asimilar facial appearance to the propositus with a flatmidface, a short, flat nose, and fleshy lips with a widemouth (Fig. 4).

The propositus’ brother (III-2) had a similar facialappearance and fifth finger clinodactyly (Fig. 4), butcardiological findings were normal.

The mother (II-2) had a flat occiput, a medial flare to

*Correspondence to: Dr. A. Slavotinek, Department of ClinicalGenetics, St. Mary’s Hospital, Hathersage Rd., Manches-ter M13 0JH, United Kingdom.

Received 23 December 1996; Accepted 6 January 1997

American Journal of Medical Genetics 71:229–232 (1997)

© 1997 Wiley-Liss, Inc.

her eyebrows, and a short philtrum (Figs. 4, 5). Shewas born with a short, flat nose requiring plastic sur-gery on 4 occasions. She had fifth finger clinodactylywith normal flexion creases. A roentgenograph of herfeet showed a bony exostosis arising from the medialaspect of the left fifth metatarsal in the same positionas the extra digit in her daughter. There was no historyof a cardiac murmur, and her adult height was 155 cm(3rd to 10th centile).

The mother’s youngest brother (II-4) had a heartmurmur as a child, and a patent ductus arteriosus wasrepaired at 3 years. He was born with a flat, short nose,but declined surgery. At 26 years, he had a flat facialprofile, synophrys, a short, grooved philtrum, and rela-tively full lips (Fig. 6). There was fifth finger clinodac-tyly. His height was 180 cm (75th centile).

His eldest daughter (III-6) was born at 41 weeks ofgestation by emergency cesarean section for fetal dis-tress with a birth weight of 2,850 g (3rd to 10th centile).A heart murmur was noted at age 4 weeks, and a pat-ent ductus arteriosus was diagnosed at 3 months.Echocardiography at 26 months showed a 6–7 mm duc-

tus, and ligation was performed. At 57⁄12 years, she hada flat occiput and midface, epicanthic folds, hypertel-orism (at age 6 years, ICD was 3.4 cm and OCD 9.5 cm),a short, flat nose with anteverted nares (Fig. 6), ashort, well-grooved philtrum, and a large mouth withduck-bill lips. There was fifth finger clinodactyly. Shewas normally grown.

Her brother (III-8) was born by normal vaginal de-livery at 39 weeks of gestation with a birthweight of2,700 g (3rd to 10th centile). Investigations for feedingdifficulties and breathlessness at age 12 days led to thediagnosis of a patent ductus arteriosus. A 7 mm patentductus arteriosus was ligated at age 7 months. At 19⁄12

year, his length was 78 cm (3rd to 10th centile) andweight was 10.3 kg (10th to 25th centile). At age 3years, he had a facial appearance similar to that of hissister and cousins (Fig. 6). He had small epicanthicfolds and hypertelorism (at age 35⁄12 years, ICD was 3.5cm and OCD 11.0 cm).

The maternal grandfather (I-2) and his father werereported to have similar noses, but there was no his-tory of cardiac disease in the grandfather. There wasno family history of learning difficulties.

DISCUSSION

Autosomal dominant inheritance of isolated patentductus arteriosus has been described in several fami-lies [Burman, 1961; Martin et al., 1986; Rogers et al.,1992; Woods and Sheffield, 1994]. However, domi-nantly transmitted patent ductus arteriosus with facialanomalies is rare. Several families with CHAR syn-drome [Char, 1978; Temple, 1992; Sletten and Pier-pont, 1995] and one with dominant inheritance of pat-ent ductus and short nose [Davidson, 1992] were re-ported previously.

Fig. 1. The family pedigree.

Fig. 2. The propositus at age 2 years 7⁄12, front view (a) and profile (b).

230 Slavotinek et al.

The eyebrow flare, flat midface and flat nasal bridge,short philtrum, and duck-bill lips in the family aretypical of CHAR syndrome, and we consider this syn-drome to be the diagnosis. However, there was no pto-sis, low-set ears, strabismus, or developmental delay.There were no abnormalities of the distal interphalan-geal joints or flexion creases. Interestingly, the facialfindings in older relatives were less pronounced, andthe duck-bill lips less prominent. This change in phe-notype with age was reported in the family describedby Temple [1992].

A distinctive anomaly in our patients that has notbeen described in any of the previously reported fami-lies was polydactyly. Patent ductus arteriosus and me-soaxial polydactyly can be found in Robinow syndrome[Balci et al., 1993; Atalay et al., 1993], but the pheno-type of this condition is different from that found inthis family. Although the shape of the nose and facialprofile in our affected family members was similar tomaxillonasal dysplasia (Binder’s syndrome), cardiac le-sions are uncommon in this condition [Quarrell et al.,1990].

Autosomal dominant inheritance of a patent ductusarteriosus has also been reported together with a flat

Fig. 3. Roentgenograph of left foot of the propositus’ sister, showinginterstitial polydactyly.

Fig. 4. Family of the propositus showing mother, sister, and brother.

Fig. 5. Profile of the propositus’ mother.

Fig. 6. The propositus’ maternal uncle with 2 of his children.

Familial Patent Ductus Arteriosus 231

facial profile, high forehead, and a short nose with abroad, flattened tip [Davidson, 1992]. Fifth finger clino-dactyly was also present in the family, but did not al-ways segregate with the cardiac lesion.

Our family illustrates the importance of a full familyhistory and careful examination of facial feature beforethe estimation of recurrence risk for patent ductus ar-teriosus. The changes in the phenotype of CHAR syn-drome with age should also be considered.

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