Journal of Pediatric Ophthalmology and Strabismus

Ocular Abnormalities in the Smith-Lemli-Opitz Syndrome

Jeffrey D Gold, MD; David D Pfaffenbach, MD

Abstract

In 1964, Smith, Lemli, and Opitz ' reported the association of epicanthus, ptosis, and strabismus in three unrelated boys with microcephaly, distinctive facies, skeletal defects, genital maldevelopment, and growth and psychomotor retardation. Fifty subsequent case reports have broadened the picture of the Smith-Lemli-Opitz (SLO) syndrome, adding the following ocular abnormalities: small palpebral fissures with antimongoloid slant, mild exophthalmos, retinal pigment epithelial defects, pale disks, nystagmus, microcornea, and aniridia.' Six patients had congenital cataracts1; successful removal in one patient led to the only report in the ophthalmologic literature of the SLO syndrome.*

The constellation of Duane's retraction syndrome, absence of lacrimal pu neta, corneal enlargement, iris deformity, and bilateral optic pits has not been previously described. The occurrence of these defects in a child with the SLO syndrome is important to the ophthalmologist as an example of ocular and somatic dysmorphogenesls manifesting during the second month of embryonic development

CASE REPORT

This eight-month-old boy was the product of a full term pregnancy in a 22-year-old, gravida 2, para 2, Latin American woman. There was a roentgen exposure at the end of the first month of gestation of one chest x-ray. The pregnancy was complicated only by a second trimester episode of cystitis, treated with su If isoxazone, phenazopyridine, and nitrofurantoin. Feeble and infrequent fetal movements were first detected late in the fifth month. No history of antenatal viral infection or exposure to teratogens could be elicited. Family history revealed unexplained neonatal deaths, psychomotor retardation, and unspecified seizures on the paternal side. Both parents and an older sibling were normal.

Parturition was normal, but the neonatal period was characterized by pneumonia with cyanosis, feeding difficulties and vomiting. Two episodes of aspiration pneumonia were accompanied by high fever with tonic-clonic seizures which have since been controlled by diphenylhydantoin and phenobarbital.

Extreme underdevelopment of the external genitalia with cryptorchidism was noted, and an orchiopexy was performed on the left at age two months. A small right indirect inguinal hernia was noted He received four injections of testosterone which were reported to have helped with phallic enlargement and rugalization of the scrotum.

Congenital glaucoma should be considered in an infant with corneal enlargement, abnormal Iris insertion, and craters in the optic nerves. Most infant corneas measure 10.5 mm in diameter, or less. When associated with tears in Descemefs membrane, a measurement over 12 mm is diagnostic of congenital glaucoma." In our patient, the corneas measured 12.5 mm, but Descemefs membrane was intact Furthermore, the optic nerves were not cupped and the intraocular pressure was normal.

The evidence is good for the abnormal embryogenesis in this child to have occurred for the most part during the second month of gestation, especially in regard to the ocular abnormalities. Each of the congenital anomalies found in this patient, and in others with the SLO syndrome, has been reported as either a sporadic or inherited condition, in various combinations. The etiology of the SLO syndrome is uncertain; however, all authors agree that inheritance either follows an autosomal recessive pattern or represents a cytogenetics I Iy undetectable chromosome abnormality. Additional reports concerning Duane's retraction syndrome, punctai atresia, anterior segment anomalies, and optic pits, in association with other congenital ocular and somatic defects will be necessary to further categorize this constellation of defects. Furthermore, ophthalmologists should be aware of the SLO syndrome, inasmuch as it may be an affected child's ocular defects which first bring him to the attention of a physician.

SUMMARY

A child with the Smith-Lemli-Opitz syndrome is described with a previously unreported constellation of congenital ocular malformations. The ocular abnormalities in this child include: Duane's retraction syndrome, short…

In 1964, Smith, Lemli, and Opitz ' reported the association of epicanthus, ptosis, and strabismus in three unrelated boys with microcephaly, distinctive facies, skeletal defects, genital maldevelopment, and growth and psychomotor retardation. Fifty subsequent case reports have broadened the picture of the Smith-Lemli-Opitz (SLO) syndrome, adding the following ocular abnormalities: small palpebral fissures with antimongoloid slant, mild exophthalmos, retinal pigment epithelial defects, pale disks, nystagmus, microcornea, and aniridia.' Six patients had congenital cataracts1; successful removal in one patient led to the only report in the ophthalmologic literature of the SLO syndrome.*

The constellation of Duane's retraction syndrome, absence of lacrimal pu neta, corneal enlargement, iris deformity, and bilateral optic pits has not been previously described. The occurrence of these defects in a child with the SLO syndrome is important to the ophthalmologist as an example of ocular and somatic dysmorphogenesls manifesting during the second month of embryonic development

CASE REPORT

This eight-month-old boy was the product of a full term pregnancy in a 22-year-old, gravida 2, para 2, Latin American woman. There was a roentgen exposure at the end of the first month of gestation of one chest x-ray. The pregnancy was complicated only by a second trimester episode of cystitis, treated with su If isoxazone, phenazopyridine, and nitrofurantoin. Feeble and infrequent fetal movements were first detected late in the fifth month. No history of antenatal viral infection or exposure to teratogens could be elicited. Family history revealed unexplained neonatal deaths, psychomotor retardation, and unspecified seizures on the paternal side. Both parents and an older sibling were normal.

Parturition was normal, but the neonatal period was characterized by pneumonia with cyanosis, feeding difficulties and vomiting. Two episodes of aspiration pneumonia were accompanied by high fever with tonic-clonic seizures which have since been controlled by diphenylhydantoin and phenobarbital.

Extreme underdevelopment of the external genitalia with cryptorchidism was noted, and an orchiopexy was performed on the left at age two months. A small right indirect inguinal hernia was noted He received four injections of testosterone which were reported to have helped with phallic enlargement and rugalization of the scrotum.

Fig. 1. Short, broad- based nose with anteverted nares. Left ptosis with short palpebral fissure.

Fig. 1. Short, broad- based nose with anteverted nares. Left ptosis with short palpebral fissure.

Our physical examination (Tables I and II) revealed a 16-pound, 4-ounce, hypotonic boy with normal head size. The neck was short and he was unable to maintain an upright head position. The nose was short with a broad base and anteverted nares (Fig. 1). The maxillary alveolar ridges were larger than normal, with resultant high, narrow palate (Fig. 2). The mandible was markedly reduced in size. The ears were posteriorly rotated with a blind fistula on each anterior helix (Fig. 3).

Fig. 2. Broad maxillary alveolar ridges with resultant high, narrow palate.

Fig. 2. Broad maxillary alveolar ridges with resultant high, narrow palate.

Fig. 3. Short, broad-based nose. Posteriorly rotated ears with blind fistula on anterior helix, micrognathism, short neck.

Fig. 3. Short, broad-based nose. Posteriorly rotated ears with blind fistula on anterior helix, micrognathism, short neck.

Both eyes demonstrated mucopurulent exudate. The left palpebral tissue was 17 mm long; the nght20 mm (Fig. 1). There was ptosis on the left. Fixation and following movements were normal. Attempted adduction of the left eye resulted in marked retraction of the globe and contraction of the palpebral fissure, which then widened on attempted abduction (limited) (Fig. 4). Forced ductions were normal. All four lacrimal puncta were absent (Fig. 5). Biomicroscopic examination revealed normal corneas and lenses, and gonioscopy revealed broad iris processes inserted to the anterior trabeculum, bilaterally (Fig. 6). Corneal diameters were 12.5 mm bilaterally. Intraocular pressure ranged from 21 to 22 mm Hg in the right eye and from 17 to 19 in the left eye. Ophthalmoscopy revealed normal size and shape optic disks, each of which contained, in its temporal aspect, a small gray oval pit, with the long axis parallel to the disk margin (Fig. 7).' The optic pits measured two diopters deep in the right disk and four diopters in the left. Both maculae were normal. Retinoscopy revealed minimal hypermetropie (OD +0.50; OS +1.00).

Both hands had mild clinodactyly of the fourth and fifth fingers, marked exaggeration of the distal palmar crease with formation of a cleft between the second and third fingers giving the appearance of a mild lobster-claw deformity. In addition, an ulnar flexion contracture at the proximal interphalangeal joint of the index fingers caused them to overlap the third fingers (Fig. 8). Dermatoglyphic evaluation was abnormal, revealing 9/10 whorls. Both wrists were deviated ulnarward. The feet had mild hammertoe deformity of the great toes, mild clinodactyly of the fifth toes, and minimal cutaneous syndactyly of the second and third toes.

FIg. 4. Top: retraction of globe and contraction of palpebral fissure of left eye on adduction. Center: primary position; bottom: limited abduction of left eye.

FIg. 4. Top: retraction of globe and contraction of palpebral fissure of left eye on adduction. Center: primary position; bottom: limited abduction of left eye.

Table

TABLE 1OCULAR ABNORMALITIES IN THE SLO SYNDROME

TABLE 1

OCULAR ABNORMALITIES IN THE SLO SYNDROME

Fig. 5. Absence of ail four lacrimal puncta. Top: right eye; bottom: left eye.

Fig. 5. Absence of ail four lacrimal puncta. Top: right eye; bottom: left eye.

The phallus measured 1.5 cm long by 0.75 cm diameter. A mild first degree hypospadias was present (Fig. 9). The left testicle was palpable high in the undersized scrotum.

Laboratory examination of blood and spinal fluid were unrevealing. Chromosome analyses and electroencephalograms at ages one and two months were normal. Both parents demonstrated normal karyotypes. Roentgenograms of the trachea and esophagus revealed no cause for the feeding problems. A persistent density in the hilar area of the right lung was interpreted as atelectasis secondary to repeated aspiration pneumonia. The heart was rotated. Roentgenograms of the extremities showed no carpal ossification centers, indicating a bone age of approximately one month (Fig. 10).

DISCUSSION

The literature contains 53 case reports of the SLO syndrome and includes several excellent reviews.' All ocular anomalies previously reported with this syndrome and those manifested by this patient are given in Table I. The majority of cases have demonstrated ptosis, epfcanthus, and convergent strabismus. Cataracts have been found in six patients. Additional ocular defects observed include: short palpebral fissure, pale optic äisks, nystagmus, retinal pigment epithelial defects, aniridia, and microcornea. The constellation of ocular abnormalities found in this child has, to our knowledge, never been reported.

The somatic anomalies found in this patient are given in Table U. The listed frequences of these anomalies among the 52 children with the SLO syndrome are only minimal estimates because of the retrospective nature of this study.

Duane's retraction syndrome, first described in 1905," has not been previously associated with punctal atresia, anterior segment anomalies, or optic pits. In 1972, Cross and Pfaffenbach " called attention to the association of the syndrome with other ocular malformations and palatal, auricular, and vertebral defects. After a review of 186 cases of Duane's syndrome, Pfaffenbach et al " concluded the basic dysgenesis occurred during the fourth to tenth week of embryonic development It is within this time frame that normal development includes the formation of the oculomotor nuclei. Fibers of the third, fourth, and sixth cranial nerves extend out from the brain stem to enter their respective muscles which are, by this time, distinctively blocked out in the paraxial mesoderm.

Fig. 6. Broad iris processes inserting to trabeculum.

Fig. 6. Broad iris processes inserting to trabeculum.

Fig. 7. Temporally placed pit In each optic nerve head. Left: right fundus; right: left fundus.

Fig. 7. Temporally placed pit In each optic nerve head. Left: right fundus; right: left fundus.

Table

TABLE IlOTHER CONGENITAL MALFORMATIONS PRESENT IN THIS CASE

TABLE Il

OTHER CONGENITAL MALFORMATIONS PRESENT IN THIS CASE

Fig. 8. Right hand showing abnormal distal palmar crease, mild claw deformity, flexion contracture of index finger.

Fig. 8. Right hand showing abnormal distal palmar crease, mild claw deformity, flexion contracture of index finger.

Fig. 9. Markedly undersized external genitalia. Penis bound down by chordee.

Fig. 9. Markedly undersized external genitalia. Penis bound down by chordee.

Over 200 cases of optic pits have been reported since Weithe first described them in 1882 ; of these only 8.5 per cent have been bilateral. Discussion of associated anomalies has been largely omitted from case reports describing optic pits; Ferry,'4 however, described cardiac, renal, skeletal, and facial abnormalities in seven patients with optic pits. Most authors accept that this congenital anomaly is due to an embryonic disturbance of the primitive epithelial papilla which is present during the fourth week of gestation.

There have been occasional reports of the absence of all lacrimal pu neta," and even more rare are papers relating punctal atresia with other anomalies. Town" reported a case of bilateral absence of upper puncta with esotropia, while Wiegmann and Walker" described a familial syndrome of true lobster-claw deformity and nasolacrimal duct obstruction. During the second month of gestation, lacrimal canaliculi form as solid epithelial cords, but have not yet reached the lid margin. Canalization is usually completed during the third month and the puncta open during the fifth month. Mann" states that punctual atresia may represent a failure of budding of the epithelial cord during the sixth to seventh week of embryonic life, or a simple failure of surface epithelial disintegration at any later time.

Fig. 10. Roentgenogram of right hand showing deformed index finger and complete absence of carpal ossification centers.

Fig. 10. Roentgenogram of right hand showing deformed index finger and complete absence of carpal ossification centers.

Congenital glaucoma should be considered in an infant with corneal enlargement, abnormal Iris insertion, and craters in the optic nerves. Most infant corneas measure 10.5 mm in diameter, or less. When associated with tears in Descemefs membrane, a measurement over 12 mm is diagnostic of congenital glaucoma." In our patient, the corneas measured 12.5 mm, but Descemefs membrane was intact Furthermore, the optic nerves were not cupped and the intraocular pressure was normal.

The evidence is good for the abnormal embryogenesis in this child to have occurred for the most part during the second month of gestation, especially in regard to the ocular abnormalities. Each of the congenital anomalies found in this patient, and in others with the SLO syndrome, has been reported as either a sporadic or inherited condition, in various combinations. The etiology of the SLO syndrome is uncertain; however, all authors agree that inheritance either follows an autosomal recessive pattern or represents a cytogenetics I Iy undetectable chromosome abnormality. Additional reports concerning Duane's retraction syndrome, punctai atresia, anterior segment anomalies, and optic pits, in association with other congenital ocular and somatic defects will be necessary to further categorize this constellation of defects. Furthermore, ophthalmologists should be aware of the SLO syndrome, inasmuch as it may be an affected child's ocular defects which first bring him to the attention of a physician.

SUMMARY

A child with the Smith-Lemli-Opitz syndrome is described with a previously unreported constellation of congenital ocular malformations. The ocular abnormalities in this child include: Duane's retraction syndrome, short palpebral fissure, ptosis, absence of all lacrimal puncta, corneal enlargement, abnormal iris insertion, and bilateral optic pits. The frequency of all reported ocular defects occurring with this syndrome is reviewed, and the possible etlologlcally significant dysmorphogenesis is discussed.

REFERENCES

1. Smith DW, Lem Ii L, Opitz JM: A newly recognized syndrome of multiple congenital anomalies. J Pedlatr 64:210-217, 1964.

2. Opitz JM, Zellweger H, Shannon WR et al: The RSH syndrome. Birth Defects 5:43-52, 1969.

3. Arey LB: Developmental Anatomy: A Textbook and Laboratory Manual of Embryology, ed 7. Philadelphia, WB Saunders Co, 1966.

4. Duke-Elder WS: System of Ophthalmology, Vol III, Pt 1, Embryology. London, Henry Kimpton, 1963.

5. Mann, I: Development of the Human Eye, ed 3. New York, Grune and Stratton Inc. 1964.

6. Smith DW: Dysmorphology (Teratology). J Pediatr 69:1150-1169, 1966.

7. Dallalre L, Fraser FC: The Smith-Lemli-Opitz syndrome of retardation, urogenital and skeletal anomalies. Birth Defects 5:180-182, 1969.

8. Fine RN, Gwinn JL, Young EF: Smith-LemliOpitz syndrome: radiologic and postmortem findings. Am J Dis Child 115:483-488, 1968.

9. Ruvalcaba RH, Reichert A, Smith DW: SmithLemli-Opitz syndrome: case report Arch Dis Child 43:620-623, 1968.

10. Duane A: Congenital deficiency of abduction, associated with impairment of adduction, retraction movements, contraction of the palpebral fissure and oblique movements of the eye. Arch Ophthalmol 34:133-159, 1905.

11. Cross HE, Pfaffenbach DD: Duane's retraction syndrome and associated congenital malformations. Am J Ophthalmol 73:442-450, 1972.

12. Pffafenbach DD, Cross HE. Kearns TP: Congenital anomalies in Duane's retraction syndrome. Arch Ophthalmol 88:635-639, 1972.

13. Weithe T: Ein Fall von augenborener Difformltat der Sehnervenpapille. Arch Augenheilk 11:14-19, 1882.

14. Ferry AP: Macular detachment associated with congenital pit of the optic nerve head. Arch Ophthalmol 70:346-357, 1963.

15. Allen JC: Congenital absence of the lacrimal punctum. J Pediatr Ophthalmol 5:176-178, 1968.

16. Town AE: Congenital absence of lacrimal pcmcia in three members of a family. Arch Cphthalmol 29:767-771, 1943.

17. Wiogmann OA, Walker FA: The syndrome of lobster claw deformity and nasolacrimal obstruction. J Pediatr Qphthalmol 7:79-85, 1970.

18. Mann I: Developmental Abnormalities of the Eye, ed 2. PhiIade~phla, JB Lippincott Co, 1957, p 389.

19. Kolker AE, Hetherington J: Becker-Shatfer's Diagnosis and Therapy of the Glaucomas, ed 3. St Louis, The CV Mosby Co, 1970, p 259.

TABLE 1

OCULAR ABNORMALITIES IN THE SLO SYNDROME

TABLE Il

OTHER CONGENITAL MALFORMATIONS PRESENT IN THIS CASE

10.3928/0191-3913-19751101-07

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