The Cornelia Delange Syndrome A Report Of Three Cases

Claude N. Lambert, M.D.


In our Orthopaedic Clinic we have recently seen three patients with unusual multiple congenital anomalies. We were unable to classify these cases adequately until a diligent search of the literature revealed an article by Louis J. Ptacek, M.D., and associates in the Journal of Pediatrics (63:1000-1020, 1963) which described six infants with the Cornelia DeLange syndrome. Our three cases fitted into this category, and thus provided us with the proper classification.

What really aroused our interest in this condition was the fact that the involved children were classified by the authors as phocomelias of the upper extremities. From the photographs the extremities did not seem to be true phocomelias. I wrote to Dr. Ptacek and requested permission to review his X-rays. He very kindly sent me pictures on two children, namely, his Cases 3 and 5.

Dr. Ptacek's Case 3 showed a relatively normal humerus, one forearm bone which was most probably a radius, a single digit, and a severe flexion contracture of the elbow. The deformities were bilateral. According to the Frantz-O'Rahilly classification, this condition would be described as bilateral terminal longitudinal complete paraxial hemimelia: ulnar, or, in other words, monodigital hands.

His Case 5 showed a normal humerus, a severe flexion contracture of the elbow, a radius (the only bone in the forearm), and two digits on the radial side which clinically looked like a small-sized thumb and index finger. This again was a terminal paraxial hemimelia: ulnar.

Our own three cases may be briefly described as follows:

Case 1

L.C. was first seen at age four-and-one-half months. Her birth weight had been 4 pounds 10 ounces. She had a marked systolic murmur and congenital anomalies of both upper extremities. There was a very low hairline, markedly bushy hair, eyebrows low and continuous across the nasal bridge, and, in addition to the loud cardiac murmur, slight cyanosis. X-rays showed that the lower extremities were normal.

X-rays of the upper extremities revealed a relatively normal humerus, radius, and ulna, but a partial adac-tylia on the right side. On the left, the clinical appearance was that of an elbow-disarticulation amputation. However, roentgenographs showed a humerus and radius, but with the radius flexed completely and covered with the same skin as the humerus, thus giving the clinical appearance described above. There was total absence of ulna and hand bones (Fig. 1 Fig. 2 and 3 ).

Nothing was done prosthetically at this time, but at approximately one year of age the patient was reevaluated relative to her cardiac condition, the impression being that she had ventricular septal and atrial septal defects. The patient also had cardiomegaly. Cardiac catheterization was performed. Because of the mental retardation present, the child was discharged at age one year to the State Psychiatric Institution and has not returned to the clinic.

Case 2

J.A. was first seen at age ten days. Birth weight was 5 pounds 5 ounces. A 15-month-old sibling had been born with congenital dislocation of both hips and both knees. Physical examination showed that the ears were low bilaterally, the eyes were small, and hypertelorism was noted. The child had cleft lip and cleft palate, complete. A linear midline frontal ridge and a prominent frontal suture were present.

The upper extremities showed bilateral phocomelias-the right lower, a phocomelia, and the left lower, phocomelia, distal incomplete (Fig. 4 , Fig. 5 and Fig. 6 ). Nothing was done with this child at that time, but at age four months he was returned to the hospital for correction of his harelip and cleft palate. He had a marked elevation of temperature and was discharged. However, he returned three months later, at which time the plastic repair of the bilateral cleft lip was done. The child was lost to follow-up and of course was never fitted with a prosthesis.

Cornelia C. DeLange was one of the pioneer medical women of the Netherlands. She started general practice in Amsterdam, later going to Zurich, where she specialized in pediatrics. She returned to Amsterdam and in 1927 became Professor of Pediatrics in the Faculty of Medicine of the University of Amsterdam, the first woman in the Netherlands to acquire a full professorship. She wrote her first article in 1897 on "Comparative Analysis of Ashes." She became known for her work in neuroanatomy and gained an international reputation. In 1938 she retired but continued her scientific work both in neuroanatomy and in pediatrics.

Dr. DeLange reported the first two documented cases of the syndrome that now bears her name. Its chief factors include microbrachycephaly; anomalies of both upper and lower extremities, phocomelia and paraxial ulnar hemimelia being most common; characteristic facies; and an unusual cry, which at times is a low-pitched growl. These patients usually have to be tube-fed, are generally debilitated, and are highly susceptible to infection. The syndrome is probably genetic in character, possibly a dominant autosomal mutation.

Case 3

P.D. was first seen at the age of 13 months. She had been able to sit at age nine months, but at the age seen was unable to stand, walk, or talk. Her face was broad and flat, the eyebrows thick and joined together at the midline, and there was a decreased anteroposterior diameter of the cranium. Both upper extremities showed obvious anomalies. On the right, the humerus, ulna, and radius were relatively normal, but partial adactylia was apparent, with rays 2 and 3 missing. On the left were a relatively normal humerus, a short radius with a severe flexion contracture, and absence of rays 3, 4, and 5. In other words, on the right, partial adactylia, and on the left, terminal longitudinal paraxial hemimelia: ulnar. The lower extremities were normal (Fig. 7 and 8 )Fig. 9 and 10 .

Due to the poor life expectancy of patients with this syndrome, nothing was done at this time. However, a note was made that should the child survive, the best indicated treatment would be elbow disarticulation on the left, and then fitting with an adequate prosthesis. This child did not survive.

Conclusion

Our experiences with three children exhibiting the Cornelia DeLange Syndrome have been briefly described. These children present deficiencies of the extremities similar to those encountered in other congenital etiologies. However, because of a poor life expectancy, these children may not survive for a sufficient period to make prosthetic fitting feasible.

Claude N. Lambert, M.D. is associated with University of Illinois Amputee Clinic Chicago, Illinois