OPHTHALMO-­‐ACROMELIC   SYNDROME   WITH   TIBIAL   DEFORMITY:   CASE   REPORT  FROM  QUETTA  

MOBIN-­‐UR-­‐REHMAN1,   ASMATULLAH   DURRANI2,   SANA   BUSHRA3,   ZAMRAKA  ISMAIL4  

1Associate   Professor   Paediatrics.2,3,4   Paediatrics   Residents   Bolan  Medical   College  QueNa  

Correspondance  to  Dr  Mobin-­‐ur-­‐Rehman.  E  mail:  mobin38@gmail.com  

ABSTRACT

Ophthalmo- acromelic syndrome also called anophthalmia- Waardenburg syndrome is a rare autosomal recessive syndrome characterized by eye malformations ranging from true anophthalmia to mild micropthalmia with acromelic malformations. Herein, we present the first case of opthalmo-acromelic syndrome type Waardenburg with tibial deformity.

Key words: anophthalmia acromelic tibia recessive syndrome

CASE REPORT

A 4 months old baby boy presented to us with bilateral anophthalmia. The parents were concerned that their baby was unable to see and had prominent bones of both the legs. He was a term SVD at home and the mother had no infectious, physical or pharmacological trauma during pregnancy. However he had no additional issues, was feeding well and could hold his neck at the age of four months. He was the seventh born of consangious parents

and one of his sisters aged four years also had anophthalmia.

On physical examination his anthropometric measures were at the 3rd percentile. He had bilateral anophthalmia, oligodactyly of feet with four toes and prominent lower ends of tibia. There was no hepatosplenomegaly or rash and the cardiac exam was normal.

On laboratory investigations routine blood analysis was normal. TORCH serology was unremarkable and so was the abdominal ultrasonography. The ultrasonographic examination of the eyes revealed bilateral absence of the eye bulbs and optic nerve. The radiograph of the lower limbs showed healing fractures with callus formation at the lower end of tibia.

Discussion

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly(1). It is an extremely rare autosomal recessive syndrome and the eye malformations can range from true anophthalmia to mild microphthalmia(2). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma). The features of this condition are present from birth.

Some 29 affected individuals have been reported since

Waardenburg's first report in 1935 [Waardenburg et al., 1961](3). Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding) in eight unrelated families. Four of these mutations are nonsense, two frames-shift, and two missense(1). Others have found the locus to be at the 422-kb region at 10q11.23, based on the results from the two consanguineous families as well as the consistent data from the Japanese non-consanguineous family. The 422-kb region only contained one gene, MPP7(4). Yahyavi, M. Abouzeid, H.Gawdat, G. et al conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems(5).

The first detailed report was described by Richieri-Costa et al of 5 children of 2 different families with consanguineous parents in 1983. They highlighted the association of bilateral (in 4) or unilateral (in 1) clinical anophthalmia with multiple other congenital abnormalities, mainly in the distal parts of the limbs(6). Four years later Traboulsi et reported affected brother and sister and affected first cousin. The parents were consanguineous in the case of each affected siblings. The proband had bilateral syndactyly of the fourth and fifth toes, synostosis of the fourth and fifth metatarsals on the left, and absence of the right fifth metatarsal. (7). In the same year Pallotta and Dallapiccola described a syndrome with true anophthalmia, facial anomalies, hand and foot defects and mental retardation in three patients(8). Le Merrer et al. (1988) described 2 consanguineous sibships with 3 children and 2 children with this syndrome, respectively. The distal abnormalities of the limbs included syndactyly IV-V, fusion of metacarpals IV-V, absence of the

fifth toes, and, in the second family, hypoplasia of the fibula with short femur or tibia. Similarly Sayli et al. (1995) reported the cases of 2 brothers from a consanguineous family who had bilateral clinical anophthalmia, partial synostosis of metatarsals IV and V, and basal synostosis of the fourth and fifth toes on the right only in the older sib(9). From Turkey Suyugul et al. (1996) reported the cases of 2 girls, the offspring of consanguineous parents, who had bilateral clinical anophthalmia, upper and lower limb abnormalities, and mental retardation(10).   Workers from Lebanon in 1998 described a 12-day-old male infant, born of consanguineous parents, with clinical anophthalmia, split hand, oligodactyly, syndactyly, and polydactyly. The authors stated that these features were consistent with ophthalmoacromelic syndrome (OAS), but noted that this was the first report of 2/3 syndactyly of the fingers, metacarpal polydactyly, or lobster-claw hand deformity in OAS(11).  A second report from turkey in 2000 described an additional patient with ophthalmoacromelic syndrome. The parents were reportedly distant relatives. The patient had bi lateral cl in ical anophthalmia and typical l imb malformations. In addition, the patient had interruption of the inferior vena cava with azygos continuation, the first report of internal organ abnormalities in this condition(3).  Again a third report from turkey in reported an 8-year-old Turkish girl, born of consanguineous parents, who had bilateral clinical anophthalmia, syndactyly of the fourth and fifth fingers, and absence of the fifth toes. Psychomotor development was normal. X-ray examination revealed proximal fourth and fifth metacarpal synostosis, hypoplasia of the fifth finger, coalition of capitate and hamate, and absence of the fifth metatarsals and toes(12).  Lately Italian workers have described an Italian boy, born of second-

cousin gypsy parents, who had bilateral clinical anophthalmia, fused fourth and fifth metacarpals bilaterally with fifth fingers set at the base of the fourth, presence of 4 toes with 2-3 syndactyly, and undescended right testis. Abdominal ultrasound and renal scintigraphy revealed horseshoe kidney(13).  Teiber et al in 2007 described a 15-month-old girl with ophthalmoacromelic syndrome. She had an asymmetric face, left unilateral microphthalmia, short, hypoplastic fifth fingers with a single interphalangeal crease, and proximal implantation of the second and third toes. Radiographs of the hands revealed synostosis of the fourth and fifth metacarpals. Spine x-rays demonstrated cervical fusion and hemivertebrae. The authors stated that this was the first report of vertebral anomalies in this disorder(14).

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