American Journal of Medical Genetics 34:587-588 (1989)

Brief Clinical Report

Third Case of Pfeiffer-Type Cardiocranial Syndrome

Robert F. Stratton and David S. Parsons Departments of Pediatrics (R.F.S.) and Otolaryngology (D.S.P.), Wilford Hall USAF Medical Center, Lackland AFB, Texas

We report on a third child with a newly recog- nized craniosynostosis syndrome involving the sagittal suture. Additional findings not re- lated to the abnormal head growth include micrognathia with limited mouth opening, tracheobronchial anomalies, congenital heart defects, microphallus, cryptorchidism, and growth and mental retardation.

KEY WORDS: craniosynostosis, sagittal, sub- glottic stenosis, tracheal bron- chus, tracheobronchial mala- cia, congenital heart defect, mental retardation, growth deficiency, hypogenitalism

INTRODUCTION In 1987, Pfeiffer et al. reported on a brother and sister

with a “new” syndrome of sagittal craniosynostosis, multiple birth defects, and growth and mental retarda- tion [Pfeiffer et al., 19871. We report on a third child with the same constellation of major anomalies, establishing this as a recognizable craniosynostosis syndrome.

CLINICAL REPORT The propositus was born at term to healthy non-con-

sanguineous parents. The pregnancy was uncompli- cated except for a febrile gastroenteritis at about 3 weeks postconception and intermittent cramping with- out bleeding throughout the gestation. There were no fetal exposures except possibly from an ill family cat for the first 6 months of gestation. Routine fetal ultrasound showed a small head and large heart. Birth weight was

Received for publication April 24,1989; revision received July 5, 1989.

Address reprint requests to Col. Robert F. Stratton, Dept. of Pediatrics, Wilford Hall USAF Medical Center, Lackland AFB, TX

The views expressed herein are those of the authors and are not necessarily the views ofthe United States Air Force or Department of Defense.

Published 1989 by Alan R. Liss, Inc.

78236-5300.

2,381 g, and length was 48 cm. The following anomalies were noted at birth: a two-vessel umbilical cord, dol- ichocephaly with a small pointed occiput, apparently low-set ears, micrognathia, small chest with narrow shoulders, mid-thoracic kyphosis, microphallus, cryp- torchidism, bilateral transverse palmar creases, and bi- lateral club feet.

Subsequent panendoscopy showed no evidence of a cleft or submucous cleft palate. Subglottic stenosis, a tracheal bronchus, and tracheobronchomalacia were present. Cardiac catheterization demonstrated an atrial septa1 defect, which was repaired at age 9 months. At age 10 months, a tracheostomy was done for progressive airway obstruction. A gastrostomy tube was placed at age 15 months. Repeat cardiac catheterization at age 19 months demonstrated partial anomalous pulmonary venous return. Chromosomes studied elsewhere were reported as normal.

Examination at our institution at age 22 months showed growth retardation, with a length of 78.7 cm ( - 3 SD), and weight of 9.78 kg (< 5th centile). OFC was 45 cm ( - 4 SD). Pertinent physical findings are listed in Table I, with craniofacial features shown in Figure 1. Inner and outer canthal distances were 2.3 and 7.3 cm, respectively (25th-50th centile). The nasal bridge was flat and the nares anteverted. The upper lip was straight with a relatively smooth philtrim. Palm length was 5 cm ( - 2 SD), and middle finger length was 3.5 cm ( - 3 SD), with distal tapering of the fingers and normal finger- nails. Fingertip patterns were nine ulnar loops and one whorl. Foot length was 10 cm ( - 4 SD) with relatively long first toes and hypoplasia of all toenails.

Cranial CT scan showed a ventricular shunt, large lateral ventricles, and frontal cortical atrophy. Ophthal- mologic examination was normal. Otolaryngologic ex- amination demonstrated very small external auditory canals and the previously noted tracheobronchial anom- alies. Developmental assessment placed the child at the 3-4 month age level in all parameters that could be tested.

DISCUSSION Only the sibs reported by Pfeiffer et al. [19871 had a

similar constellation of anomalies. There was no men- tion of other airway anomalies. Their congenital heart

588 Stratton and Parsons

Fig. 1. Profile (a) and frontal (b) views of proposita at age 22 months

TABLE I. Clinical Manifestations of Pfeiffer-type Cardiocranial Syndrome

Sagittal synostosis has a 22-26% association with birth defects, with 4% being cardiac [Hunter and Rudd,

Growth retardation Mental retardation Sagittal synostosis dol-

ichocephaly Low-setisimple ears Hypertelorism Limited mouth opening Micrognathia Congenital heart disease Single palm crease Hypogenitalism Large joint contractures Zygodact yly Tracheobronchial anoma-

Pfeiffer et al. [19871 Patient 1 Patient 2

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defects consisted of atrial and ventricular septal defects and patent ductus arteriosus in the male, and tetralogy of Fallot, peripheral pulmonic stenosis, atrial septal de- fect, and azygous connection, instead of a normal infe- rior vena cava, in the female. Cohen [1988] used the name Pfeiffer-type cardiocranial syndrome for these sibs.

19771. The unique combination of defects seen in these children are an unlikely chance occurrence and proba- bly represents a single pleiotrophic gene defect. Al- though our patient’s mother had a febrile gastroen- teritis a t the time of organogenesis, which may have contributed to some of his defects, no such environmen- tal insults were reported by Pfeiffer et al. [1987]. Be- cause too few cases have been reported, and the hand- icaps make reproduction unlikely, we cannot say with assurance whether this is an autosomal recessive trait or a dominant trait with gonadal mosaicism in a parent of the patients of Pfeiffer et al. 119871. We conclude that we have confirmed the existence of this “new” rather than “private” craniosynostosis syndrome.

REFERENCES Cohen MM (1988): Craniosynostosis update 1987. Am J Med Genet

(Suppl) 4:99-148. Hunter AGW, Rudd NL (1977): Craniosynostosis. I. Sagittal synostosis:

Its genetics and associated clinical findings in 214 patients who lacked involvement ofthe coronal suture(s1. Teratology 14:185-194.

Pfeiffer RA, Singer H, Zschiesche S (1987): Sagittal craniostenosis, congenital heart disease, mental deficiency and various dysmor- phies in two s i b s A “new” syndrome? Eur J Pediatr 146:75-78.