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American Journal of Medical Genetics 45416-419 (1993) Brachymesomelia and Peters Anomaly: A New Syndrome Jane D. Kivlin, John C. Carey, and Mark A. Richey Departments of Ophthalmology (JJ).K., M.A.R.) and Pediatrics (J.C.C.), University of Utah School of Medicine, Salt Lake City, Utah We report on a child with an unusual meso- melic bone dysplasia and Peters anomaly. While there is some resemblance to the radio- graphic findings and corneal clouding de- scribed by Pillay in the OMMD (ophthalmo- mandibulo-melic dysplasia) syndrome, there are also differences. The several syndromes that combine brachymesomelia and corneal clouding are discussed. o 1993 Wiley-Liss, Inc. KEY WORDS: Peters anomaly, mesomelic dysplasia, corneal opacities INTRODUCTION Mesomelic dysplasia and Peters anomaly are both rare conditions. We present a patient with brachy- mesomelia and Peters anomaly and review the perti- nent syndromes. CLINICAL REPORT A 2-day-old girl was referred to the University of Utah for examination of corneal clouding and multiple congenital anomalies. The patient was a term baby of a normal pregnancy with no known drug exposure. The delivery was complicated by meconium aspiration and initial respiratory distress (Apgar scores 2 and 3). The patient's mother, a 20-year-old healthy primagravida, has a relatively small mandible and a prominent elbow point, but both are thought to be normal variants. Roentgenograms of the mother's upper limbs were nor- mal, without radial bowing, ulnar shortness, or Mad- elung deformity. The father is healthy and had a nor- mal, unaffected daughter from a previous marriage. Both parents have normal eyes. Other family history included a paternal uncle with mental retardation, and a maternal cousin with inwardly turned feet. There was no family history of eye problems, including glaucoma. There was no consanguinity. Received for publication December 3, 1990; revision; received August 21, 1992. Address reprint requests to Jane D. Kivlin, M.D., at her present address: Eye Institute, Medical College of Wisconsin, 8700 W. Wisconsin Avenue, Milwaukee, WI 53226. 0 1993 Wiley-Liss, Inc. The patient's birthweight was 2,880 g (lo%), and OFC 36.5 cm (90%). Her length was 45.5 cm (< 2%), and her upper to lower segment ratio was 2.03 (normal is 1.7). Her skull was elongated, with a flattened forehead and double hair whorls. Her mandible was normal; her ears were asymmetrical, the neck was short, and the nipples were widely spaced. The distal limbs were notably short, consistent with mesomelic dysplasia. Upper limb findings included elbow extension limited to 150" and ulnar hand deviation. The hands were of normal size. The fourth finger showed camptodactyly, and the fifth finger was rotated along the long axis and turned toward the palm. The thumb was long, with decreased thenar eminence. In the lower limbs there was decreased muscle mass, with limitation of extension at the knees to 160". The patient also had bilateral hip dislocation and talipes equinovarus with cavus defor- mity. The films showed a short and bowed radius and a markedly short, thickened ulna (Fig. l), confirming the presence of mesomelic dysplasia. The tibia and fibula were relatively short, but not to the extent seen in the ulna (Fig. 2). Other roentgenograms including spine and pelvis were normal. Ocular examination showed bilateral corneal cloud- ing, which was more severe on the left (Fig. 3A,B).The corneal diameters were approximately 11 mm (irregu- lar limbal region), within normal limits. Intraocular pressure was elevated in the borderline range at 24 mm Hg on the right and 29 mm Hg on the left with a Schiotz tonometer. The eyes were further examined under gen- eral anesthesia. The right eye had a large peripheral corneal opacity with associated anterior iris synechiae. The right eye was otherwise normal, with a clear central cornea, deep anterior chamber, clear lens, and normal fundus. The left eye had a large ring of dense opacity with areas of broad peripheral anterior synechiae. The central cornea was extremely hazy, preventing a good view of the fundus. The clear lens was not attached to the cornea. Gonioscopy showed iris strands extending up to Schwalbe's line and to the cornea. The corneal and ante- rior chamber anomalies were consistent with Peters anomaly. A 6 mm penetrating keratoplasty was performed on the patient's left cornea to restore vision when the pa- tient was 18 days old. The iris could not be separated from the corneal opacity, and much of the central iris was removed.

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  • American Journal of Medical Genetics 45416-419 (1993)

    Brachymesomelia and Peters Anomaly: A New Syndrome J a n e D. Kivlin, J o h n C. Carey, and Mark A. Richey Departments of Ophthalmology (JJ).K., M.A.R.) and Pediatrics (J.C.C.), University of Utah School of Medicine, Salt Lake City, Utah

    We report on a child with an unusual meso- melic bone dysplasia and Peters anomaly. While there is some resemblance to the radio- graphic findings and corneal clouding de- scribed by Pillay in the OMMD (ophthalmo- mandibulo-melic dysplasia) syndrome, there are also differences. The several syndromes that combine brachymesomelia and corneal clouding are discussed. o 1993 Wiley-Liss, Inc.

    KEY WORDS: Peters anomaly, mesomelic dysplasia, corneal opacities

    INTRODUCTION Mesomelic dysplasia and Peters anomaly are both

    rare conditions. We present a patient with brachy- mesomelia and Peters anomaly and review the perti- nent syndromes.

    CLINICAL REPORT A 2-day-old girl was referred to the University of

    Utah for examination of corneal clouding and multiple congenital anomalies. The patient was a term baby of a normal pregnancy with no known drug exposure. The delivery was complicated by meconium aspiration and initial respiratory distress (Apgar scores 2 and 3). The patient's mother, a 20-year-old healthy primagravida, has a relatively small mandible and a prominent elbow point, but both are thought to be normal variants. Roentgenograms of the mother's upper limbs were nor- mal, without radial bowing, ulnar shortness, or Mad- elung deformity. The father is healthy and had a nor- mal, unaffected daughter from a previous marriage. Both parents have normal eyes. Other family history included a paternal uncle with mental retardation, and a maternal cousin with inwardly turned feet. There was no family history of eye problems, including glaucoma. There was no consanguinity.

    Received for publication December 3, 1990; revision; received August 21, 1992.

    Address reprint requests to Jane D. Kivlin, M.D., a t her present address: Eye Institute, Medical College of Wisconsin, 8700 W. Wisconsin Avenue, Milwaukee, WI 53226.

    0 1993 Wiley-Liss, Inc.

    The patient's birthweight was 2,880 g (lo%), and OFC 36.5 cm (90%). Her length was 45.5 cm (< 2%), and her upper to lower segment ratio was 2.03 (normal is 1.7). Her skull was elongated, with a flattened forehead and double hair whorls. Her mandible was normal; her ears were asymmetrical, the neck was short, and the nipples were widely spaced. The distal limbs were notably short, consistent with mesomelic dysplasia.

    Upper limb findings included elbow extension limited to 150" and ulnar hand deviation. The hands were of normal size. The fourth finger showed camptodactyly, and the fifth finger was rotated along the long axis and turned toward the palm. The thumb was long, with decreased thenar eminence. In the lower limbs there was decreased muscle mass, with limitation of extension at the knees to 160". The patient also had bilateral hip dislocation and talipes equinovarus with cavus defor- mity. The films showed a short and bowed radius and a markedly short, thickened ulna (Fig. l), confirming the presence of mesomelic dysplasia. The tibia and fibula were relatively short, but not to the extent seen in the ulna (Fig. 2). Other roentgenograms including spine and pelvis were normal.

    Ocular examination showed bilateral corneal cloud- ing, which was more severe on the left (Fig. 3A,B). The corneal diameters were approximately 11 mm (irregu- lar limbal region), within normal limits. Intraocular pressure was elevated in the borderline range at 24 mm Hg on the right and 29 mm Hg on the left with a Schiotz tonometer. The eyes were further examined under gen- eral anesthesia. The right eye had a large peripheral corneal opacity with associated anterior iris synechiae. The right eye was otherwise normal, with a clear central cornea, deep anterior chamber, clear lens, and normal fundus. The left eye had a large ring of dense opacity with areas of broad peripheral anterior synechiae. The central cornea was extremely hazy, preventing a good view of the fundus. The clear lens was not attached to the cornea. Gonioscopy showed iris strands extending up to Schwalbe's line and to the cornea. The corneal and ante- rior chamber anomalies were consistent with Peters anomaly.

    A 6 mm penetrating keratoplasty was performed on the patient's left cornea to restore vision when the pa- tient was 18 days old. The iris could not be separated from the corneal opacity, and much of the central iris was removed.

  • Peters Anomaly 417

    Fig. 1. Radiograph of the right upper limb, showing bowing and shortness of the radius and marked shortness and distinct thickening of the ulna.

    The corneal graft has remained clear without rejec- tion. Intraocular pressure has remained in the bor- derline range, and the optic nerves have remained nor- mal. Because she was very hyperopic (+7.25 right, +7.50 + 5.00 x 70 left) at age 4, glasses were pre- scribed, but she has been reluctant to wear them. Visual acuity at age 6 years was 20/40 OD and 20/70 0s. Since the optical axis of each eye is clear and she does not have strabismus, her visual loss is probably due to depriva- tion amblyopia in each eye, worse on the left. Treatment is still in progress.

    Psychomotor development is normal, and she is a bright child with normal intelligence. On follow-up ex- ams, disproportionate short stature with brachy- mesomelia has persisted (Fig. 4). At age 3.5 years, her height was 79.6 cm (height age 17 months), her span was 67 cm, and her OFC was 50.6 cm (50%).

    Ocular Pathology Light microscopy of the left cornea showed a hyper-

    cellular stroma and an area of complete absence of Des-

    Fig. 2. Radiograph of the left lower limb, showing shortness of tibia and fibula without bowing.

    cemets membrane and endothelium, diagnostic of Pe- ters anomaly. Bowmans membrane was thickened, at the junction of the peripheral opacity and the central somewhat clearer cornea, to 16-22 pm (normal 10 pm, range 8-14 pm [Spencer, 1985; Kayes and Holmberg, 196011, but tapered centrally until it was absent. Where it was absent, the corneal stromal keratocytes extended up to the epithelial basement membrane. These find- ings in Bowmans membrane in Peters anomaly have been reported previously [Fogle et al., 1978; Kenyon, 19751.

    DISCUSSION Mesomelic dysplasia syndromes can be categorized

    into numerous types, each representing different radio- graphic and clinical findings [Taybi, 19831. In reviewing the radiographic manifestations in these different types, we found the mesomelic dysplasia in our patient to be unique, particularly the dysplasia involving the forearm with its unusual radial bowing, as well as the shortness and distinctive thickening of the ulna. Be-

  • 418 Kivlin et al.

    Fig. 4. The patient at age 12 months.

    Fig. 3. A Right eye. Note large peripheral corneal opacity with anterior iris synechia. B. Left eye. Note dense ring opacity of the cornea with less dense central area.

    cause of these radial and ulnar findings, we can elimi- nate the more common syndromes of mesomelic dyspla- sia from the differential diagnosis. The association of mesomelic dysplasia with congenital corneal clouding has been reported in the 5 conditions listed below. We have not included the SC or pseudothalidomide syn- drome because it is a malformation syndrome rather than osteochondrodysplasia, and corneal opacification is not consistent [Herrmann et al., 19691.

    1. Brachymesomelic-renal syndrome is characterized by shortness of the forearm and shank, and radial and ulnar bowing, with ulnar deviation (mesomelic dyspla- sia), glomerulocystic renal dysplasia, corneal opacities, and abnormalities of the vertebral bodies, cranium, and face [Langer et al., 19831. Death in early infancy results from renal failure. Our patient has had no renal abnor- malities, nor was her facial appearance similar to that seen in this syndrome.

    2. Acromesomelic dysplasia includes several forms of short-limb dwarfism in which the shortness affects the forearms and legs, as well as the hands and feet [Ohba et al., 1989; Reinhardt and Pfeiffer, 1967; Borrelli et al., 1983; Langer et al., 1977, 1989; Brahimi et al., 1988; Maroteaux et al., 19711. Of the subtypes of acro-

    mesomelic dysplasia, only the Langer type [Langer et al., 19771 has a forearm similar to that of our patient [Hall et al., 1980; Langer et al., 1977; Espiritu et al., 19751. However, our patient had normal-size fingers and a very different shank. Infrequently, corneal opacities have been described in the Langer type, but the descrip- tions have not been consistent with Peters anomaly [Langer et al., 19773.

    The forearm of 2! patients described by Fryns et al. [19881 is similar but the patients did not have leg in- volvement and thus, were ofnormal height They also did not have apparent eye involvement.

    3. Mietens syndrome shows a clinical pattern of men- tal retardation, growth failure, flexion contracture of the elbows, abnormally short ulnae and radii, bilateral cor- neal opacities, nystagmus, strabismus, and a small pointed nose [Mietens and Weber, 1966; Waring and Rodrigues, 19801. However, the corneal opacities in this syndrome have been characterized as sclerocornea [Waring and Rodrigues, 19801. And, while the forearm bones in this syndrome are short, they do not show the bowing or distinctive ulnae seen in our patient [Mietens and Weber, 19661.

    4. Short-limb dwarfism with Peters anomaly is an autosomal recessive disorder with distinctive face and rhizomelic dwarfism [Frydman et al., 19911. While the upper limbs are short, they are not bowed. Peters anom- aly has been demonstrated histopathologically. The fa- cial appearance is different from that of our patient. 5.Ophthalmo-msmdibulo-melic dysplasia (OMMD) is

    an autosomal dominant condition with congenital cor-

  • Peters Anomaly 419

    Frydman M, Weinstock AL, Cohen HA, Savir H, Varsano I (1991): Autosomal recessive Peters anomaly, typical facial appearance, failure to thrive, hydrocephalus, and other anomalies: Further delineation of the Krause-Kivlin syndrome. Am J Med Genet 40: 34-40.

    Fryns JP, Hofkens G, Fabry G, van den Berghe H (1988): Isolated mesomelic shortening of the forearm in father and daughter: A new entity in the group of mesomelic dysplasias. Clin Genet 3357-59.

    Hall CM, Stoker DJ, Robinson DC (1980): Acromesomelic dwarfism. Br J Radiol 53:999.

    Herrmann J, Feingold M, Tuffli GA, Opitz JM (1969): A familial dys- morphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: The pseudothalidomide or SC-syndrome. Birth Defects 5:81.

    Kayes J, Holmberg A (1960): The fine structure of Bowmans layer and the basement membrane of the corneal epithelium. Am J Ophthal- mol 50:1013--1021.

    Kenyon KR (1975): Mesenchymal dysgenesis in Peters anomaly, scle- rocornea and congenital endothelial dystrophy. Exp Eye Res 21: 125--142.

    Langer LO Jr, Beals RK, Solomon IL, Bard PA, Bard LA, Rissman EM, Rogers JG, Dorst JP, Hall JG, Sparks RS, Franken EA Jr (1977): Acromesomelic dwarfism: Manifestations in childhood. Am J Med Genet 1:87.

    Langer LO Jr , Nishino R, Yamaguchi A, Ito Y, Ueke T, Togari H, Kato T, Opitz JM, Gilbert EF (1983): Brachymesomelia-renal syndrome. Am J Med Genet 1557.

    Langer LO Jr, Cervenka J , Camargo M (1989): A severe autosomal recessive acromesomelic dysplasia, the Hunter-Thompson type, and comparison with the Grebe type. Human Genetics 81:323--328.

    Maroteaux P, Martinelli B, Campailla E (1971): Le nanisme acro- mesomelique. Presse Med 79:1839.

    Mietens C, Weber H (1966): A syndrome characterized by corneal opacity, nystagmus, flexion contracture of the elbows, growth fail- ure, and mental retardation. J Pediatr 69524.

    Ohba K, Ohdo S, SonodaT, Madokoro H (1989): Acromesomelic dyspla- sia in a father and son: Autosomal dominant inheritance. Acta Paediatrica Japonica Overseas Edition 31595-599.

    Pi1,lay VK (1964): Ophthalmo-mandibulo-melic-dysplasia: An heredi- tary syndrome. J Bone Joint Surg [Am] 46:858.

    Fkinhardt K, Pfeiffer RA (1967): Ulno-fibulare Dysplasie. Eine autoso- mal-dominant verebte Mikromesomelie aehnlich dem Nievergelt- syndrom. Fortschr Roentgenstr 107:379-391.

    Spencer WM (1985): Ophthalmic Pathology, Vol. 1. Philadelphia: WB Saunders, p 232.

    Taybi H (1983): Radiology of Syndromes and Metabolic Disorders. 2nd ed. Chicago: Year Book Medical Publishers, pp 105,217, 244- 247.

    Waring GO, Fbdrigues MM (1980): Ultrastructure and successful ker- atoplasty of sclerocornea in Mietens syndrome. Am J Ophthalmol 90:469.

    neal opacification and varying degrees of mandibular and mesomelic limb shortness. The only report of this syndrome was by Pillay [19641 of a man and his son and daughter. The short ulna and short, bowed radius in this family were unique. The tibiae and fibulae were also moderately short, but not bowed. The corneal opacities were bilateral in the 3 cases, with complete opacification in the father and daughter, and peripheral opacification with some central vision in the son. Through a clear portion of cornea in the son, remnants of the pupillary membrane could be seen. Histopathologic examination of the cornea was not done; however, the clinical findings are compatible with Peters anomaly. However, unlike our patient, Pillays patients had micrognathia with obtuse angles of the jaws and temporomandibular joint fusion, and apparently normal height.

    While the findings of our patient most closely resem- ble those of the patients described by Pillay and Langer, there are some differences. With small numbers of pa- tients, it is not possible to know the full range of findings in a syndrome. The inheritance of our patients condition is also not known.

    ACKNOWLEDGMENTS This study was supported in part by an unrestricted

    grant from Research to Prevent Blindness, Inc., New York, NY, to the Eye Institute, Department of Opht,hal- mology, Medical College of Wisconsin, Milwaukee, WI.

    REFERENCES Borrelli P, Fasanelli S, Marini R (1983): Acromesomelic dwarfism in a

    child with an interesting family history. Pediatr Radiol 13:165-- 168.

    Brahimi L, Bacha L, Kozlowski K, Massen R, Zenati M (1988): Acro- mesomelic dysplasia-a new type. Report of two siblings. Pediatr Radiol 18:67-69.

    Campailla E, Martinelli, B (1971): Deficit staturale con micromeso- melia. Minerva Ortop 22180-184.

    Espiritu C, Chen H, Woolley PV Jr (1975): Mesomelic dwarfism as the homozygous expression of dyschondrosteosis. Am J Dis Child 129:275.

    Fogle JA, Green WR, Kenyon KR, Naquin S, Gadol J (1978): Peripheral Peters anomaly: A histopathologic case report. J Ped Ophthalmol Strabismus 15:71-.76.