Background
Microcephalic primordial dwarfism comprises a group of rare disorders characterized by extreme growth failure [
1]. Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II) is the most common type, for which the clinical characteristics have been well described. It has been demonstrated that mutations in the pericentrin (PCNT) gene are associated with MOPD II [
2,
3]. The PCNT gene, located on 21q22.3, encodes the PCNT protein. Dysfunction of the PCNT protein leads to disorganized mitotic spindles and missegregation of chromosomes [
4], which affects cell division during growth. Diagnosis of MOPD II is usually made clinically based on the typical features although a molecular analysis of PCNT is an alternative tool to confirm the diagnosis in some cases [
5]. Herein, we report three isolated cases clinically diagnosed as MOPD II sharing similar ophthalmic features. Data regarding cycloplegic refraction, best corrected visual acuity, a slit lamp examination, ocular coherence tomography (OCT), and fundus photography are recorded.
Discussion
MOPD II is an autosomal-recessive disorder characterized by microcephaly, short stature, characteristic facial features, and abnormal dentition [
5‐
7]. Based on the facial characteristics described in the literature [
5,
7,
8], these three unconsanguineous patients had a similar bird-headed facial appearance with a broad, receding forehead, long peaked nose, high nasal bridge, maxillary protrusion, low-set prominent ears, extreme retromicrogenia, and normal-sized teeth, suggesting that they were experiencing the same disease. They also presented the same ocular manifestations, with the maculopathy and extremely short axial length associated high hyperopia. They were the only members of their family with the condition. The cases discussed here were classified as a variant of MOPD 2 because they didn’t have intrauterine growth retardation. Therefore, a higher body height was noted compared to the previous cases presented in the literature [
5,
6,
9]. In addition, they all had normal size teeth and normal intelligence, which was different from the cases discussed in the literature [
6,
7,
10,
11].
The previous two cases did not have neurological symptoms and signs until the present time. Case 1 was an adult, which is rare in MOPD II
5. Case 2 had acquired alopecia, which was not present in the other two cases. Case 3 had moyamoya disease resulting in one episode of a cerebral infarct, which was compatible with an MOPD II diagnosis. The association of moyamoya disease and MOPD II has been well demonstrated [
12‐
14]. Waldron et al. also revealed that 25% of patients with MOPD II have intracranial moyamoya and aneurysms [
13]. In addition, Bober et al. followed 25 MOPD II patients undergoing neurovascular screening tests, and found that 13 (52%) of the patients had moyamoya and/ or intracranial aneurysms [
14]. Moyamoya disease results from occlusion of the blood vessels due to extensive fibrocellular intimal thickening [
15] . It starts from the stenosis of the large arteries, which is progressive and subsequently stimulates compensated growth of small collateral vessels with a “puff-of-smoke” appearance in angiography, the so-called “moyamoya disease.” These cerebrovascular problems expose MOPD II patients to a higher risk of stroke [
14,
16], as was the case with case 3. Thrombolytic therapy is not recommended in moyamoya patients with only one stroke episode since hemodynamic problems rather than thrombus formation and embolization pose a risk of hemorrhage in areas of moyamoya collateral vessels [
17]. The parent of this child was concerned about the risk and refused embolization.
Ocular manifestations in MOPD II have rarely been reported. Far-sightedness has been found in some patients with MOPD II [
4]. However, there is a paucity of studies addressing ophthalmological findings in these patients. Bang and colleagues described “ocular moyamoya” in a 5 year-old boy with MOPD II presenting unilateral cerebral vascular moyamoya disease and ipsilateral iris collateral vessels [
18]. There are two cases in the literature documented with abnormal retinal pigmentation, one with a macular scar and the other one with retinal vascular changes [
7]. In our study, all of the subjects had atrophic macular scarring and normal retinal pigmentation. The mechanism of macular scarring in these patients is still unknown. During long-term follow-up, Case 1 had mild change in the pigmentation of the macular scar.
Case 3 and her parents had received a genetic analysis of the PCNT gene, but there were no positive result yields even after conducting a whole genomic study. Unlike the previously presented cases [
5], these three children had normal birth weight and normal sized teeth. Mutations other than PCNT gene might be the reason for their symptoms although they were diagnosed clinically as having MOPD II.
Acknowledgements
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