Seckel syndrome is an inherited autosomal recessive disorder that is part of the microcephalicprimordial dwarfism group of syndromes. The characteristic features of this syndrome are short stature, microcephaly (due to premature synostosis), prominent beaked nose, receding chin, and mental retardation. Reported ocular abnormalities include strabismus, telecanthus, small palpebral fissures, and bulging eyes.1,2 Spontaneously dislocated lenses have been reported in several congenital anomalies, the most prevalent of which are Marfan syndrome, homocystinuria, Weill- Marchesani syndrome, and Ehlers- Danlos syndrome.3 To the best of our knowledge, no report of lens dislocation in Seckel syndrome appears in the literature.
A 7-year-old girl with Seckel syndrome presented to our clinic because of acute pain, redness, and blurred vision in her right eye. The diagnosis of Seckel syndrome was based on intrauterine growth retardation, dwarfism, microcephaly, dislocation of the hip joint, hypoplastic external genitalia, mental retardation, and typical facial features. Her complaints started acutely on the day of admission. Her basic optical correction was myopic.
Figure: Dislocated lens in the posterior chamber of the right eye.
On examination, best corrected visual acuity was hand movements with full light projection in the right eye and 3-m finger counting with full light projection in the left eye. Her intraocular pressure was 30 mm Hg in the right eye and 14 mm Hg in the left eye. In the right eye, marked ciliary injection, corneal epithelial edema, a shallow anterior chamber, and a fixed mid-dilated pupil with an anteriorly dislocated lens captured in it were observed (Figure). The fundus was normal. The left lens was fully dislocated, moving freely on the anterior vitreal face. During the following days it moved several times between the anterior and the posterior chambers. The results of the rest of the ocular examination of the left eye were within normal limits.
Once the right eye had been quieted with local and systemic corticosteroids and antihypertensive agents, a pars plana Iensectomy and vitrectomy was performed. The same operation was performed on the left eye 1 week later. In the absence of any retinal pathology, no encircling band was added.
A medical investigation was performed during the patient's hospitalization. The existence of markedly elevated plasma levels of homocysteine (202 nmol/mL; upper limit of normal, 15 nmol/mL) and methionine (333 nmol/mL; upper limit of normal, 54 nmol/mL) was interpreted as evidence for homocystinuria caused by cystathionine β-synthase deficiency. The patient's parents were first cousins, and she had one sister and one brother.
The 8-year-old sister was of normal stature and had dark hair and normal intellectual development. In her enzymatic profile, evidence for enzymatic deficiency similar to that observed in the patient was found. On clinical ophthalmic examination, bilateral lens subluxation presenting as iridophacodonesis was observed. The results of the rest of the sister's ocular examination were within normal limits.
The brother looked normal, had no enzymatic deficiency, and the results of his ocular examination were normal.
We were unable to find previously reported evidence for an association between Seckel syndrome and either lens dislocation or homocystinuria. However, a previous report raises the possibility of the existence of a subgroup of patients with Seckel syndrome who have hematologic abnormalities.4 This possibility, based on clinical observations and genetic studies, is of special interest regarding the current report. Both our patient and her sister had laboratory evidence of homocystinuria, yet neither had the features typical of this disease (eg, tall stature, fair hair, and mental retardation). One might argue that in our patient's case, the features of Seckel syndrome overruled the clinical appearance. However, her sister also did not have "homocystinuric" features.
The possibility exists that the laboratory evidence for homocystinuria is related to Seckel syndrome by close genetic location. In that case, the sister should have a milder variant of the syndrome with only partial clinical expression. The reason for lens subluxation- dislocation in homocystinuria is unclear. If some homocystinuric features can be included in Seckel syndrome, then lens dislocation may be one of them. The fact that the sister had her lenses subluxated - a milder form of zonular pathology related to the dislocation found in the patient - may support her having a milder form of Seckel syndrome.
We speculate that once the diagnosis of Seckel syndrome is made in a child, the search for additional metabolic abnormalities is not always performed. The issue exists whether our patient (and the laboratory findings in her sister's investigation) presents only a coincidental occurrence of two different inherited diseases or points to homocystinuric features of Seckel syndrome. This issue cannot be resolved with our current knowledge. Because only an active search for homocysteine metabolism abnormalities in patients with Seckel syndrome can clarify this issue, we recommend that such searches be routinely performed in the future.
1. Jones KT... Smith's Recognizable Patterns of Human Malformation, 5th ed. Philadelphia: W. B. Saunders; 1997:94-95.
2. Thompson E, Pembrey M. Seckel syndrome: an overdiagnosed syndrome. J Med Genet. 1985;22:192-201.
3. Rabinowicz M. Amblyopia. In: Harley RD, ed. Pediatric Ophthalmology, 2nd ed. Philadelphia: W. B. Saunders; 1983:301302.
4. Butler MCi, Hall BD, Maclean RN, Lozzio CB. Do some patients with Seckel syndrome have hematological problems and/or chromosome breakage? Am J Med Genet. 1987;27:645-649.