Orthopedics

FETAL HYDANTOIN SYNDROME: AN UNUSUAL CAUSE OF HIP DYSPLASIA

Robert T Trousdale, MD

Abstract

The association of congenital anomalies with maternal use of anticonvulsant medicine is well-documented and has been referred to as fetal hydantoin syndrome. The most common orthopedic manifestations of this syndrome are digital hypoplasia affecting the ulnar digits and lateral toes most severely. Hip dysplasia associated with maternal ingestion of hydantoin has been mentioned, but little is in the literature concerning management of such a patient. This case report is presented to illustrate a less common orthopodic manifestation of fetal hydantoin syndrome, namely hip dysplasia.

CASE REPORT

A 23-year-old adopted man presented with a 15-year history of increasing right hip pain. The patient's biologic mother was diagnosed with a seizure disorder at approximately 1 month of gestation and placed on phenytoin therapy. The patient otherwise had an uncomplicated vaginal birth. He began having vague bilateral hip discomfort at approximately 8 years of age. Radiographs were never obtained as a child, and the patient's pain was attributed to "growing pains." The patient's left hip discomfort increased in severity to a point where he was unable to work as a custodian for an 8-hour shift. The pain was activityrelated and localized to the groin region. He denied any locking, catching, or giving way. Anti-inflammatory agents decreased but did not eliminate the discomfort.

Pertinent physical findings included the following: mild mental retardation, fingers and toes that were tapered distally with hypoplastic fingernails (the ulnar fingers and lateral toes were affected most severely) (Fig 1 ). The patient had a mild limp and leg lengths were equal. The hip was irritable on examination with marked apprehension with hip external rotation and hyperex tension. Range of motion of the right hip versus the left hip was as follows: flexion, 1307130°; extension, 20720°; external rotation, 40760e; internal rotation, 30720°; abduction, 40740°; and adduction, 20720°. Anteroposterior and false profile radiographs revealed bilateral hip dysplasia; the left hip was worse than the right (Fig 2). The femoral head was uncovered laterally as well as anteriorly. The hip center was lateralized, and a large anterolateral acetabular cyst was best seen on the false profile view.

The patient underwent a Bernese periacetabular osteotomy secondary to symptomatic dysplastic hip (Fig 3). The patient's postoperative course has been uneventful- He is presently back to full activities without any hip discomfort.

This case illustrates a patient with fetal hydantoin syndrome whose primary presenting feature was hip dysplasia. Surgical correction with acetabular osteotomy provided pain relief with marked improvement in femoral head coverage.

1. Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet. 1968; 2:1296. Letter to the editor.

2. Hanson J, Smith D. The fetal hydantoin syndrome. J Pediatr. 1975; 87:285-290.

3. Barr M Jr, Poznanski A. Schmickel R. Digital hypoplasia and anticonvulsants during gestation - a teratogenic syndrome? J Pediatr. J 974; 84:254-256.

4. Hanson J, Myrianthopoulos N, Harvey M, Smith D. Risks to the offspring of women treated with hydantoin anticonvulsants with emphasis on the fetal hydantoin syndrome. J Pediatr. 1976: 89:662-668.

5. Hill R. Fetal malformations and antiepilepttc drugs. Am J Dis Child. 1976; 130:925.

6. International Symposium on Phenytoin - Induced Teratology and Gingival Pathology. J Am Dent Assoc. 1979:99:652-655.

7. Kogutt MS. Fetal hydantoin syndrome. South Med J. 1984; 77:657-658.

8. Kousseff BG, Stein M. Fetal hydantoin syndrome. Am J Dis Child. 1981; 135:371-372.

9. Loughnan P, Gold H, Vance J. Phenytoin teratogenicity in man. Lancet. 1972; 1:70-72.

10. Lowe C. Congenital malformations among infants born to epileptic women. Lance/. 1973; 1:9-10.

11. Massey K. Teratogenic effects of diphenylhydantoin sodium. J Oral Ther Pharm. 1966;2:380-385.

12. Mouson R, Rosenberg L. Hartz S, Shapiro S, Heinonen O, Slone D. Diphenylhydantoin and…

The association of congenital anomalies with maternal use of anticonvulsant medicine is well-documented and has been referred to as fetal hydantoin syndrome. The most common orthopedic manifestations of this syndrome are digital hypoplasia affecting the ulnar digits and lateral toes most severely. Hip dysplasia associated with maternal ingestion of hydantoin has been mentioned, but little is in the literature concerning management of such a patient. This case report is presented to illustrate a less common orthopodic manifestation of fetal hydantoin syndrome, namely hip dysplasia.

CASE REPORT

A 23-year-old adopted man presented with a 15-year history of increasing right hip pain. The patient's biologic mother was diagnosed with a seizure disorder at approximately 1 month of gestation and placed on phenytoin therapy. The patient otherwise had an uncomplicated vaginal birth. He began having vague bilateral hip discomfort at approximately 8 years of age. Radiographs were never obtained as a child, and the patient's pain was attributed to "growing pains." The patient's left hip discomfort increased in severity to a point where he was unable to work as a custodian for an 8-hour shift. The pain was activityrelated and localized to the groin region. He denied any locking, catching, or giving way. Anti-inflammatory agents decreased but did not eliminate the discomfort.

Pertinent physical findings included the following: mild mental retardation, fingers and toes that were tapered distally with hypoplastic fingernails (the ulnar fingers and lateral toes were affected most severely) (Fig 1 ). The patient had a mild limp and leg lengths were equal. The hip was irritable on examination with marked apprehension with hip external rotation and hyperex tension. Range of motion of the right hip versus the left hip was as follows: flexion, 1307130°; extension, 20720°; external rotation, 40760e; internal rotation, 30720°; abduction, 40740°; and adduction, 20720°. Anteroposterior and false profile radiographs revealed bilateral hip dysplasia; the left hip was worse than the right (Fig 2). The femoral head was uncovered laterally as well as anteriorly. The hip center was lateralized, and a large anterolateral acetabular cyst was best seen on the false profile view.

The patient underwent a Bernese periacetabular osteotomy secondary to symptomatic dysplastic hip (Fig 3). The patient's postoperative course has been uneventful- He is presently back to full activities without any hip discomfort.

Fig 1 : Clinical photograph of the patient's hands (left) and feet (right). Note the distal digital hypoplasia affecting ulnar fingers and lateral toes most severely.

Fig 1 : Clinical photograph of the patient's hands (left) and feet (right). Note the distal digital hypoplasia affecting ulnar fingers and lateral toes most severely.

Fig 2A: Preoperative AP pelvis radiographs. The patient has bilateral hip dysplasia with uncovered femoral heads. Note the abnormal acetabular index and lateralized femoral head.

Fig 2A: Preoperative AP pelvis radiographs. The patient has bilateral hip dysplasia with uncovered femoral heads. Note the abnormal acetabular index and lateralized femoral head.

DISCUSSION

Meadow1 was the first to suggest a possible link between maternal ingestion of anticonvulsants and congenital anomalies. Hanson and Smith2 used me term "fetal hydantoin syndrome" to describe children of mothers who ingested hydantoin anticonvulsants afflicted with a broad multisystem pattern of abnormalities including mental retardation, craniofacial anomalies, and prenatal onset growth deficiency. Digital hypoplasia, irregular ossification of the distal phalanges with nail dystrophy, coarse profuse scalp hair, hirsutism, short neck, abdominal hernias, cardiac abnormalities, and pilonidal sinus also have been associated with maternal ingestion of hydantoins.3-19

This patient's predominant manifestations of fetal hydantoin syndrome were mild mental retardation, distal digital hypoplasia, and hip dysplasia. In fact, the association of his momer's ingestion of phenytoin was not brought to light until his hip pain became severe enough to precipitate orthopedic referral.

Fig 2B: False profile radiograph showing extremely poor anterior coverage. Cysts are present in the anterior acetabulum.

Fig 2B: False profile radiograph showing extremely poor anterior coverage. Cysts are present in the anterior acetabulum.

When hip dysplasia is symptomatic, surgical intervention is warranted. Improving femoral head coverage with articular cartilage will provide pain relief and may prevent me development of secondary arthritis by increasing the joint contact area. In the majority of dysplastic hips, including this case, the acetabular anatomy is more severely affected than the proximal femur. Surgical correction should be focused on the acetabular side of the joint. If the triradiate cartilage is closed, the Bernese periacetabular osteotomy is our preferred technique because this osteotomy allows anterior and lateral coverage of the femoral head and medialization of the hip center to all be performed through a single anterior approach. The osteotomies are straight and relatively reproducible. The posterior column of the hemipelvis remains intact, allowing early ambulation and requiring minimal internal fixation (Fig 3).20,21

Fig 3A: Postoperative AP radiograph showing improvement of acetabular index angle and medialization of the hip center of rotation.

Fig 3A: Postoperative AP radiograph showing improvement of acetabular index angle and medialization of the hip center of rotation.

Fig 3B: Postoperative false profile radiograph showing marked improvement in anterior femoral head coverage.

Fig 3B: Postoperative false profile radiograph showing marked improvement in anterior femoral head coverage.

This case illustrates a patient with fetal hydantoin syndrome whose primary presenting feature was hip dysplasia. Surgical correction with acetabular osteotomy provided pain relief with marked improvement in femoral head coverage.

REFERENCES

1. Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet. 1968; 2:1296. Letter to the editor.

2. Hanson J, Smith D. The fetal hydantoin syndrome. J Pediatr. 1975; 87:285-290.

3. Barr M Jr, Poznanski A. Schmickel R. Digital hypoplasia and anticonvulsants during gestation - a teratogenic syndrome? J Pediatr. J 974; 84:254-256.

4. Hanson J, Myrianthopoulos N, Harvey M, Smith D. Risks to the offspring of women treated with hydantoin anticonvulsants with emphasis on the fetal hydantoin syndrome. J Pediatr. 1976: 89:662-668.

5. Hill R. Fetal malformations and antiepilepttc drugs. Am J Dis Child. 1976; 130:925.

6. International Symposium on Phenytoin - Induced Teratology and Gingival Pathology. J Am Dent Assoc. 1979:99:652-655.

7. Kogutt MS. Fetal hydantoin syndrome. South Med J. 1984; 77:657-658.

8. Kousseff BG, Stein M. Fetal hydantoin syndrome. Am J Dis Child. 1981; 135:371-372.

9. Loughnan P, Gold H, Vance J. Phenytoin teratogenicity in man. Lancet. 1972; 1:70-72.

10. Lowe C. Congenital malformations among infants born to epileptic women. Lance/. 1973; 1:9-10.

11. Massey K. Teratogenic effects of diphenylhydantoin sodium. J Oral Ther Pharm. 1966;2:380-385.

12. Mouson R, Rosenberg L. Hartz S, Shapiro S, Heinonen O, Slone D. Diphenylhydantoin and selected congenital malformations. N Engl J Med. 1973;289:1049-1052.

13. Niswander J. Wertelecki W. Congenita) malformation among offspring of epileptic women. Lancet. 1973; 1:1062.

14. Ramilo J, Harris UJ. Neuroblastoma in a child with the hydantoin and fetal alcohol syndrome. The radiographic features. Br J Radiol. 1979;52:993-999.

15. Seeler RA, Israel JN, Royal JE. et al. Ganglion neuroblastoma and fetal hydantoinalcohol syndromes. Pediatrics. 1979; 63:524-527.

16. Smitil D. Recognizable Patterns of Human Malformation. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1976.

17. Smith D. Teratogenicity of anticonvulsive medications. Am J Dis Child. 1977; 131:1337-1339.

18. Speidel B, Meadow SR. Maternal epilepsy and abnormalities of the fetus and the newborn. Lancet. 1972; 2:839-843.

19. Zellweger H. Anticonvulsants during pregnancy - A danger to the developing fetus? Clin Pediatr. 1974; 13:38-345.

20. Ganz R. Klaue K, Vinh TS. Mast JW. A new periacetabular osteotomy for the treatment of hip dysplasia. Technique and preliminary results. Clin Orthop. 1988; 232:26-36.

21. McGrory BJ, Trousdale RT, Cabanela ME, Ganz R. Bernese periacetabular osteotomy. Surgical technique. J Orthop Tech. 1993; 1:187.

10.3928/0147-7447-19980201-20

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