The Fanconi Syndrome
Charles H. Frantz, M.D. John Burr, M.D.
In 1927 Fanconi (1) described three brothers with multiple congenital abnormalities who developed a fatal aplastic anemia at approximately five years of age.
Since that time, well over one hundred cases of the Syndrome have been reported. In Fanconi's original description, the family involved consisted of five children - the three affected brothers and two normal siblings. The involved children typically developed bleeding episodes with fever and infection. Since this syndrome is encountered infrequently, the presence of three cases in the Area Child Amputee Center at the same time was thought to be quite unusual. These three cases are the subject of this report.
Case No. 1
D.J., female, born 4/26/60. In July 1961 this fifteen months old child was transferred to our care. Clinically this child presented interesting malformations: left upper complete phocomelia and right intercalary radial hemimelia with severe shortening, and severe internal torsion of the tibiae with knee flexion contractures. The hips were normal.(Figs. 1A and 1B).
Before being transferred to us, this patient had been seen on several occasions by the referring pediatrician, Dr. Julius Rutzky of Pontiac, Michigan. Dr. Rutzky had diagnosed her condition as a hypoplastic thrombocytopenia with persistent decrease in megakaryocytes on repeated bone marrow biopsies.
This diagnosis, in conjunction with the clinical picture of malformations.clearly indicated a Fanconi syndrome, and subsequent studies bore out all of the primary blood findings. Interestingly enough, our main problem with this child was in getting her to ambulate. The marked internal torsion of the tibiae called for bilateral de-rotation osteotomies and stretching plasters. However, we were warned against any surgical procedure because of the thrombo-penia. Repeated attempts by the pediatric service to bring her average 10,100 platelets up to a near-normal level by various means, including cortical steroids, failed.
Under these circumstances, the child was placed in hip flexion-knee flexion corrective braces with the feet externally rotated (Figs. 1C, 1D, and 1E ). Following partial correction of the internal torsion, long leg wedging plasters were applied serially, eventually obtaining extension of 160-170 degrees. This child is now ambulatory and is being seen every two months. She does have recurrent purpuretic spots.
Prosthetic applications to the upper extremity limbs have been postponed since the child has acceptable function without prostheses. (She can grasp objects bilaterally or transfer them from hand to hand, and can bring either hand to her mouth.)
Case No. 2
J.S., male, born 7/20/61. This patient was first seen at the age of twenty months. He has bilateral complete upper phocomelia with four digits and a rudimentary thumb (Fig. 2 ). His history revealed that at the age of one and one-haIf months he had developed extensive hemorrhagic areas over his body and had undergone a splenectomy. At the time of the splenectomy the platelet count was found to be less than 5,000. The last platelet count in June 1963 was 74,200.
Eventually he was fitted with a left upper prosthesis incorporating an open humeral section through which the left phoco-melic digit could manipulate a manual lever for elbow operation. This child now lives in Samoa with his missionary parents.
Case No. 3
J.H., male, born 6/22/59. This child was first seen at the Area Child Amputee Center at four years of age. He was referred from Montana. He is the oldest of three children, the two younger siblings being normal. Marked shortening of the forearms was noted at birth.
Clinical evaluation revealed the classical picture of bilateral intercalary radial hemimelia (Fig. 3 ). His detailed history indicated that he had been found to have a thrombopenia at the age of six months, with the platelet count reported as being 39,000. No surgery was performed on this child, and the parents were unable to tell us if he had had hemorrhagic episodes or petechiae. In June 1964 the platelet count was 72,000.
Because of his minimal handicap, the only treatment provided this boy was training in daily living activities in the Occupational Therapy Department. As of June 1964 J.H. was not experiencing any particular functional difficulty, nor was there any clinical evidence of complications from his Fanconi syndrome.
It is interesting to note that in April 1959 Shaw and Oliver (2) of the University of London reported Fanconi syndrome in male siblings. Both children were found to have marked bilateral radial hemimelia with severe shortening. The younger one also had severe internal tibial torsion. In the older sibling, the platelet count did not go above 3,600. He expired at the age of eight months from cerebral hemorrhage. The younger sibling initially demonstrated a platelet count of 40,000 and bone marrow studies showed absence of megakaryocytes. The younger one underwent a number of whole blood transfusions and the platelet count was raised to 105,000. At the time of reporting, he was alive and healthy.
Pertinent studies have been made on platelet counts in premature infants.
Medoff (3) studied twenty-six premature infants, repeating platelet counts weekly until the infants attained the age of thirty days or over. The smaller infants repeatedly demonstrated less than 50,000 platelets between the tenth and twentieth days of postnatal life. Larger infants tended to have a higher platelet count, most of them over 100,000.None of the larger babies demonstrated bleeding tendencies.
Thalidomide Not Implicated
Drug ingestion as a possible etiological factor could not be positively proven in any of the three cases reported by the Area Child Amputee Center, and none of the families had ever heard of thalidomide .
Because of the rarity of the condition exemplified by these three cases, correspondence was initiated in late September 1964 with Dr. Widukind Lenz of Hamburg, Germany, relative to the incidence of Fanconi syndrome in West Germany during the thalidomide episode. Dr. Lenz stated that in 980 cases of thalidomide malformations there were no cases of Fanconi' s syndrome. In one case of confirmed thalidomide history, platelets temporarily dropped to between 50,000 - 100,000, but later were found to be normal.
Blood Studies Recommended
This condition, rare as it is, may very likely appear in child amputee centers with a significant caseload of children with malformations. It would seem wise, therefore, to make complete blood studies of these youngsters, including platelet counts, especially if there is a probability of surgical correction.
Charles Frantz and John Burr are associated with the Area Child Amputee Center, Michigan Crippled Children Commission, Grand Rapids, Michigan
John Burr is Lt. Cmdr. USNMC, U.S. Naval Hospital, Long Beach, California
1. Fanconi, G.: Famiiiare infantile perniziosaartige anamie (Pernizio-sis Blutbild und Konstitution), Jahrbuch Kinderh. 117:257. 1927.
2. Shaw, S. and Oliver, R.A.M.: Congenital hypoplastic thrombocytopenia with skeletal deformities in siblings. "Blood" 14:374-377. April 1959.
3. Medoff, H.S. : Platelet counts in premature infants. J. Pediat. 64: 287-289. 1964.