J Clin Ultrasound 14:463-465, July/August 1986 Case Report

Sonographic Diagnosis of Cloverleaf Skull and Thanatophoric Dysplasia in the

Second Trimester

Carl P. Weiner, MD,* Roger A. Williamson, MD,* and Stephen M. Bonsib, MDP

An infant with thanatophoric dysplasia occurs in approximately 1:6,400 deliveries.' This lethal, sporadically occurring condition is readily diag- nosable prenatally with ultrasound.2 The risk of recurrence is negligible since there are no docu- mented cases involving sibs (Judith G. Hall, MD, personal communication). However, should than- atophoric dysplasia be associated with a "clover- leaf'' skull (Kleeblattschadel), the inheritance pattern is presumed autosomal recessive in some families with a recurrence risk of 1/4.3 We report the second-trimester diagnosis of cloverleaf skull with thanatophoric dysplasia confirmed following pregnancy termination. Classic features of the disorder were documented sonographically.

CASE REPORT

A 23-year-old gravida 3, para 1 was referred to the University of Iowa Prenatal Diagnosis Clinic at 22 weeks of gestation for evaluation of a size-date discrepancy. On ultrasound examination (ADR4OOO SL, 3.0-MHz transducer), a cloverleaf skull was apparent (Figure 1). The chest was markedly con- tracted in comparison to the abdomen (Figure 2). The femur length (23 mm) was more than 4.5 stan- dard deviations below the mean value for gesta- tional age. The shaft was thickened and bowed (Figure 3). Both the patient and her husband were counseled concerning the lethal nature of the con- dition. The couple elected to abort the pregnancy.

The prenatal diagnosis of thanatophoric dys- plasia associated with cloverleaf skull was con- firmed following a saline termination. The

Departments of *Obstetrics and Gynecology, Division of Ma- ternal-Fetal Medicine, and tPathology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. For reprints contact Carl P. Weiner, MD, Department of Obstetrics and Gynecol- ogy, University of Iowa Hospitals, Iowa City, Iowa 52242.

0 1986 by John Wiley & Sons, Inc. 0091 -2751/86/060463-03 $04.00

crown-heel length of the abortus was 28.5 cm. Short upper and lower extremities were apparent (Figure 4). A cloverleaf cranium resulted from synostosis of the coronal and lambdoidal sutures with bulging temporal bones and confluence of the anterior and posterior fontanelles. The heart con- tained a membranous ventricular septa1 defect.

FIGURE 1. Coronal image (occipital-mental) of a cloverleaf skull with the configuration secondary to synostosis of the coronal, lambdoidal and metopic sutures and open squamosal suture. Curved white arrow, bulge through the open squamosal sutures; solid white arrow head, occiput; open white arrow, mentum.

463

FlGURE2. Longitudinal view of thorax and abdomen revealing marked thoracic compression (black arrows demarcate posterior wall).

flGURE 4. Frontal view demonstrating cloverleaf deformity, con- stricted thorax, and extremely short limbs.

FIGURE 3. Femur length of 23 mm. Shaft displays the typical thickened and bowed image (open white arrows). JOURNAL OF CLINICAL ULTRASOUND

CLOVERLEAF SKULL AND THANATOPHORIC DYSPLASlA 465

Microscopic examination of the ribs, vertebral body, and proximal femur showed uneven epiphyseal growth plates with disordered and/or deficient chondrocyte maturation and focal fibrous bands traversing the growth plate; each is characteristic of thanatophoric dysplasia.

DISCUSSION

The association and genetic implications of than- atophoric dysplasia with cloverleaf skull were first reported by Partington and associates in 1971.4 Although rare, the syndrome must be distin- guished from thanatophoric dysplasia alone. The mode of inheritance is controversial but may rep- resent a n autosomal recessive trait. Two previous case reports presented some of the sonographic findings, but neonatal radiologic findings and as- sessment were required for d i a g n ~ s i s . ~ . ~

As discussed in depth by C ~ h e n , ~ the cloverleaf skull malformation may be an isolated finding or associated with several monogenic craniosynos- tosis syndromes, amniotic bands, or other unique but not fully characterized malformation pat- terns. Thus, the diagnosis of cloverleaf skull should trigger an intensive ultrasound investigation for other anomalies as an aid to effective counseling and management decisions. Should the patient who has borne a n infant with thanatophoric dysplasia and cloverleaf skull conceive again, a level-2 early second-trimester ultrasound is indicated because

of the possible 114 recurrence risk. Since the fetal skull is well formed by 16 weeks of gestation, ab- sence of a cloverleaf malformation after 16 weeks should preclude a recurrence. We would also rec- ommend ultrasound for those couples who have had a child with thanatophoric dwarfism without cloverleaf skull deformity. The reassurance af- forded by such an examination justifies the procedure.

REFERENCES

1. Smith DW: Recognizable Patterns of Human Mal- formation (ed 3). Philadelphia, WB Saunders, 1982, p 242.

2. Filly RA, Golbus MS: Ultrasonography of the normal and pathologic fetal skeleton. Radio1 Clin North Am 20:311, 1982.

3. Cohen MM: Genetic perspectives on craniosynostosis in syndromes with craniosynostosis. J Neurosurg 47:886, 1977.

4. Partington MW, Gonzales-Crussi F, Khakee SG, et al: Cloverleaf skull and thanatophoric dwarfism. Re- port of four cases, two in the same sibship. Arch Dis Child 46:656, 1971.

5. Burrows PE, Stannard MW, Pearrow J, e t al: Early antenatal sonographic recognition of thanatophoric dysplasia with cloverleaf skull deformity. Am J Roentgen01 143:841, 1984.

6. Chervenak FA, Blahemore KJ, Issacson G, et al: Antenatal sonographic findings of thanatophoric dysplasia with cloverleaf skull. Am J Obstet Gynecol 146:984, 1983.

VOL. 14, NO. 6, JULYfAUGUST 1986