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American Journal of Medical Genetics 44:562-566 (1992)

Acrania: A Manifestation of the Adams-Oliver Syndrome

David Chitayat, Catherine Meunier, Kathy A. Hodgkinson, Laura Robb, and Michael Azouz Department of Pediatrics, Diuiswns of Medical Genetics (D.C., C.M., KA.H. , L.R.) and Radiology ( M A .), Montreal Children$ Hospital and Centre for Human Genetics, McGill Uniuersity, Montreal, Quebec, Canada

A 10-year-old male with acrania, distal limb anomalies, and abnormal arterial and venous cranial blood vessels is reported. Parental films and examination are normal. This case supports the hypothesis that acrania is a severe form of aplasia cutis congenita and is within the spectrum of Adams-Oliver syndrome. It is proposed that the diagnosis of acrania requires assessment of both parents and proband to assess other manifestations of vascular disruption in order to provide accu- rate genetic counselling. o 1992 Wiley-Liss, Inc.

KEY WORDS: transverse terminal limb anomalies, vascular disruption, aplasia cutis congenita

Fig. 1. The patient shortly after birth. Note the skull and scalp defect over the fronto-parieto-occipital area.

INTRODUCTION Adams-Oliver syndrome (AOS) is an autosomal domi-

nant condition comprising congenital scalp defects with distal limb anomalies in which both inter and intra- familial variability, and other manifestations of fetal vascular disruption, occur [Adams and Oliver, 1945; Scribanu and Temtamy, 1975; Hidalgo et al., 1983; Toriello et al., 19881.

Acrania is a rare congenital anomaly in which the flat bones of the cranial vault are absent, although the bones at the base of the skull are normally present. The patho- genesis of this abnormality is unknown, but it may be the result of abnormal migration of mesenchyme under the calvarian ectoderm [Vergani et al., 19871. A patient with acrania and distal limb deficiency is reported, the association of which suggests AOS.

CLINICAL REPORT This 10-year-old boy was born at term after an uncom-

plicated pregnancy and delivery, to healthy, unrelated 27-year-old French-Canadian parents with a noncon- tributory family history. Apgar scores were 9 and 10 at one and 5 minutes, respectively. Birth weight was 3,300

Received for publication August 22, 1991; revision received April 13, 1992.

Address reprint requests to Dr. D. Chitayat, The Hospital for Sick Children, Departments of Pediatrics and Genetics, 555 Uni- versity Avenue, Toronto, Ontario, Canada M5G 1x8.

0 1992 Wiley-Liss, Inc.

g (50-75th centile), length 47 cm ( - 2 SD), and OFC 31 cm (< - 2 SD). A skull, scalp, and dural defect was noted involving most of the parieto-occipital region extending to the frontal bone, exposing the arachnoidal tissue. There was a short sloping forehead, broad nasal bridge, simple ears with large floppy pinnae, hypoplastic supra- orbital ridges and malar areas, and a high arched palate (Fig. 1). The distal phalanges of the right 2nd-4th, and left 1st-5th fingers were short and there was limited flexion in the distal interphalangeal joints. Toes were rudimentary, with absent distal phalanges and partial syndactyly (Figs. 2, 3). There were 2 symmetrical an- giomatous lesions on the abdominal wall at the T11 level. Chromosomes were normal (46,XY) and both amnion and chorion were intact with no evidence of amniotic bands.

After initial failed attempts to cover the defect with amnion, a skin graft succeeded and a helmet provided for protection. Tonic clonic seizures began at 4l/2 months, followed by 2 convulsive attacks at 4 and 5 years after mild head trauma. Electroencephalograms (EEGs) showed epileptiform activity over the left temporal and frontal regions. Brain stem auditory evoked responses were normal.

Skull films showed the extent of the defect which included the frontal bone (more apparent on the right), the parietal bone, and the upper part of the occipital bones (Fig. 4). Brain computed tomography (CT) scan at birth was normal, although at 7 weeks, prominent cere- brospinal (CSF) spaces were noted. A brain ultrasound

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Fig. 2. The patient’s hands and feet. Note the absence of terminal phalanges and syndactyly of the toes.

Fig. 4. The patient’s skull film. Note the defect including almost all the membranous skull.

Fig. 3. Films of the patient’s hand (A) and feet (B).

study at 5 years documented a previously unseen cyst (2 x 3.5 cm) and subdural effusion in the right frontal area.

Carotid angiography at 8 and 9 years showed an un- usual radiating pattern of the middle cerebral artery (Fig. 5A). The superior saggital sinus was absent, and venous drainage was through large tortuous cortical veins draining into the sphenoparietal and transverse sinuses (Fig. 5B,C). The internal cerebral vein and straight sinus were demonstrated only by means of a left internal carotid artery injection. The middle meningeal arteries and superficial temporal arteries failed to fill and covered only the lower half of the skull on the right and the lower third on the left.

Heart was normal on examination, although echocar- diogram showed an asymptomatic bicuspid aortic valve.

At 10 years, his height is 131 cm (10-25th centile), weight 29.4 kg (2540th centile), and OFC 47.5 cm (< - 2 SD). Psychomotor development, which had origi- nally showed delay in coordination and fine motor development, now shows borderline delay.

Parental films of skull and limbs are normal.

DISCUSSION Acrania is a rare congenital anomaly in which the

bony cranial vault is missing [Pilotti and Gubbetta, 19711. The flat bones which comprise the skull are formed in the 4th week of embryological development [O’Rahilly et al., 1986; Sadler, 19851. It has been sug- gested that acrania results from failure of migration of specific mesenchymal tissue, the membranous neurocranium, around the sides and top of the brain. The basal part of the fetal skull is derived from cartilaginous neurocranium, and the facial bones from membranous viscerocranium. In acrania, these tissues are present and undergo normal ossification [Mannes et al., 19821.

Acrania has been observed in a variety of clinical situations, including trisomy 13 lScribanu and Tem-

564 Chitayat et al.

Fig. 5. The patient’s carotid angiography: note the small caliber of the superficial temporal artery (A) and the absent superior sagittal sinus with the abnormal venous drainage (B, C).

tamy, 19751, congenital infection, amniotic bands and extrinsic pressure, or trauma [Argenta and Dingman, 19861. Acrania is always associated with aplasia cutis congentia (ACC), although only 10% of ACC cases in- volve the skull [Spear and Mickle, 1982; Argenta and Dingman, 19861. The presumed underlying mechanism is a vascular disruption of developing blood vessels with

a selective effect on membranous neurocranium. In a recent report, calvarial hypoplasia was found in association with intrauterine exposure to angiotensin convert- ing enzyme inhibitor. In this case, it is probably related to severe fetal hypotension during the second and third trimester [Brent and Beckman, 19911.

The frequency of abnormalities associated with acra-

Acrania 565

nia is unknown. Brain mieration disorders [cox et al.. Brent RL. Beckman DA (1991): Aneiotensin-convertinaenzvme inhibi- 1985; Kalousek et al., 19501, and multiple-associated problems including metatarsus varus, bilateral cleft lip, and absence of the orbital floor have been reported [Mannes et al., 1982; Vergani et al., 19871.

AOS was first reported in 1945 in a 3 generation family tAdams and Oliver, 19451. The presence of terminal transverse defects and ACC with a spectrum of vari- able underlying bone defects together suggests a more generalized disorder of vascular development. Support- ing evidence for this comes from the association of AOS with other vascular disruption abnormalities including the Poland sequence [Der Kaloustian et al., 19911 and the association of Poland sequence with other vascular disruption conditions such as Sprengel’s deformity, Klippel-Feil, and Mobius anomalies [Van Allen, 1981; Bouwes Bavinck and Weaver, 19861.

The primary vascular defect probably results in an abnormal blood supply to susceptible areas such as the scalp, brain, pectoralis muscle, and terminal limbs [Sol- tan and Holmes, 19861. The present case represents the most severe form of AOS in which the bony defect in- volves the whole cranial vault. In this child, both the arterial supply and venous drainage were grossly abnormal. In most cases of familial AOS and other vascular disruption sequences, the mode of inheritance is autoso- ma1 dominant [Bonafede and Beighton, 1979; Burton et a]., 1976; McMurray et al., 1977; Rosenbaum, 1951; Scribanu and Temtamy, 1975; Wilson and Harcus, 1982; Kuster et al., 19881 although single cases [Pincherele, 1938; Ollivier and Janvier, 1969; Farmer and Maxmen, 1960; Fryns, 1987; Irons and Olsen, 1980; Sybert, 19891 as well as affected sibs born to normal parents have been reported [Kahn and Olmedo, 1950; Koiffmann et al., 19881. These latter cases may be due to a variably pene- trant, variably expressive autosomal dominant gene [Fraser et al., 19891.

Fetal ultrasound studies may be used to diagnose acrania prenatally. Some of these cases may previously have been misdiagnosed as anencephaly due to extreme brain trauma at delivery. In such cases the recurrence risk may be underestimated and investigations looking for limb reduction defects (LRD) may be indicated for both proband and parents, including ultrasound mon- itoring of future pregnancies. As LRD may be the only abnormality in AOS, these same investigations may be considered for individuals with LRD.

In conclusion this case represents the most severe form of ACC (acrania) associated with AOS, and the cranial vascular abnormalities support the hypothesis that AOS results from vascular disruption.

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