Unusual acrofacıal dysostosıs wıth severe limb defects: A new syndrome

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1 GENETIC COUNSELING, Vol. 22, No 3, 2011, A. Karaman pp et al., Acrofacial dysostosis with limb defects Unusual acrofacıal dysostosıs wıth severe limb defects: A new syndrome By A. Karaman 1 and H. Kahveci 2 Summary: Unusual acrofacial dysostosis with severe limb defects: a new syndrome: The acrofacial dysostoses are a heterogeneous group of disorders characterised by defects in craniofacial and limb development. The hallmarks include downward slanting palpebral fissures, malar hypoplasia, and retrognathia combined with variable limb malformations. We report the patient, a 5-day-old-boy with craniofacial dysmorphic features and upper and lower limb defects respectively. Key-words: Acrofacial dysostoses Micrognathia Limb defects. ıntroductıon The acrofacial dysostoses (AFD) are heterogenous disorders combining varying severities of mandibulofacial dysostosis with pre and/or postaxial limb abnormalities. Malar hypoplasia and lower lid ectropion have been found in all patients. Micrognathia is the rule and this tends to improve with age. Cleft palate has been present in several cases. The predominantly preaxial form is called Nager AFD and the predominantly postaxial form is called Miller syndrome (8, 11). Here we present a patient with distinct facial features, and with profound limb defects. CLINICAL REPORT The mother was a 39-year-old gravida 3 abortus 0 married to a 38-yearold man. The parents were nonconsanguineous. Pregnancy history was negative for exposure to drugs or teratogens. This male infant was born after an uneventful term pregnancy and delivery, with a birth weight of 2200g. The maxillofacial malformation was diagnosed after birth, including marked micrognathia and malar hypoplasia, dysplastic ear lobes, atresia of the external ear canals, antimongoloid slanting of the eyes without coloboma of the eyelids, a short soft palate with a hypoplastic epiglottis, and a small tongue. The neck was wide as if webbed (Figs 1A, B, and 2). Radiographs of the upper and lower limb showed (1) Department of Medical Genetics, Erzurum Nenehatun Obstetrics and Gynecology Hospital, Erzurum, Turkey. (2) Neonatal Intensive Care Unit, Erzurum Nenehatun Obstetrics and Gynecology Hospital, Erzurum, Turkey. 249

GENETIC COUNSELING A B Figure 1A, B: Facial appearance of the

lobes Figure 2: Appearance of the patient A B Figure 3:

hypoplastic ulna on one side is present (A).

2 GENETIC COUNSELING A B Figure 1A, B: Facial appearance of the patient: Note micrognathia, malar hypoplasia, and dysplastic ear lobes Figure 2: Appearance of the patient A B Figure 3: Radiographs of case s right arm: Radiohumeral synostosis, with a hypoplastic ulna on one side is present (A). Radiographs of case s left arm: Radial hypoplasia, with a hypoplastic ulna on one side is present (B) 250

3 A. Karaman et al., Acrofacial dysostosis with limb defects Figure 4: The lower limb appearance of the case. Figure 5: Radiographs of case s limb: The left femur is absent and the right fibula is absent. 251

4 GENETIC COUNSELING profound major abnormalities. The patient had right radiohumeral synostosis, with a hypoplastic ulna on one side and left radial hypoplasia, with a hypoplastic ulna on one side (Fig 3A, B). The lower limb had left femural aplasia and right fibular aplasia (Figs 4 and 5). Laboratory examinations and karyotype analysis were normal. The case had no abnormal organs on ultrasound examination. A computerized tomography demonstrated a normal brain. He had patent ductus arteriosus on echocardiographic examination. Family history was unremarkable. Dıscussıon Limb defects, particularly preaxial anomalies, are of diagnostic significance in Nager syndrome, and serve to differentiate this condition from mandibulofacial dysostosis. Heterogeneity of apparently non-syndromal acrofacial dysostosis of both types (Nager and Treacher-Collins) is powerful support for the hypothesis that the acrofacial dysostosis (AFD)s are polytopic field defects arising during blastogenesis (4, 6, 10). Micrognathia is the rule and this tends to improve with age. Cleft palate has been present in several cases (4, 10). Several syndromic entities have been described in the literature namely Miller syndrome, which must be differentiated from Treacher Collins and Nager syndromes (6). The majority of patients with preaxial acrofacial dysostosis syndrome appear to represent sporadic occurrences. Nevertheless, substantial evidence supports an autosomal recessive pattern of inheritance and or dominant inheritance (4). Limb defects can occur in connection with other forms of syndromic associations. Unilateral defects occurred with anomalies suggesting VACTERL association, facio-auriculo-radial anomaly, and CHILD S syndrome (3, 5, 7). Bilateral defects occurred more often in genetic or potentially genetic disorders such as ectrodactyly-ectodermal dysplasia-tibial aplasia, oromandibular-limb syndrome, and intercalary defects (1, 2, 9). An unusual association of AFD and upper and lower limb major abnormalities that has not yet been described is reported in our paper. Our case had right radiohumeral synostosis, with a hypoplastic ulna on one side and left radial hypoplasia, with a hypoplastic ulna on one side. The lower limb showed left femural aplasia and rigth fibular aplasia. Thompson et al. (12) reported a case of preaxial acrofacial dysostosis with tetralogy of Fallot. Our case had patent ductus arteriosus. Most cases of AFD have been sporadic. However, seven cases of parent-to-child transmission have been documented, suggesting autosomal dominant inheritance for some cases; and six families in which 252

5 A. Karaman et al., Acrofacial dysostosis with limb defects unaffected parents have given birth to more than one affected child have been reported, suggesting autosomal recessive inheritance for others (8). References 1. Al Kaıssı A., Csepan R., Klaushofer K., GrIll F.: Femoral-tibial-synostosis in a child with Roberts syndrome (Pseudothalidomide). Cases Journal, 2008, 1, Al Kaıssı A., Grıll F., SafI H., Ben Ghachem M., Ben ChehIda F., Klaushofer K.: Craniocervical junction malformation in a child with Oromandibular-limb hypogenesis-möbius syndrome. Orphanet J. Rare Dis., 2007, 2, Basel D., Goldblatt J.: Tibial aplasia VAC- TERL association, a new syndrome? Clin. Dysmorphol., 2000, 9, Bonthron D.T., Macgregor D.F., Barr D.G.D.: Nager acrofacial dysostosis: minor familial manifestations supporting dominant inheritance. Clin. Genet., 1993, 43, Chrıstıansen J.V., Petersen H.O., Sogaard H.: The CHILD syndrome congenital hemidysplasia with ichthyosiform erythroderma and limb defects. A case report. Acta Derm. Venereol., 1984, 64, DIxon M.J.: Treacher Collins syndrome. Hum. Mol. Genet., 1996, 5, HardIng A.E., Hall C.M., BaraItser M.: Autosomal dominant asymmetrical radial dysplasia, dysmorphic facies, and conductive hearing loss (facioauriculoradial dysplasia). J. Med. Genet., 1982, 19, Jones K.L.: Smith s Recognizable Patterns of Human Malformation. 6th edn. Philadelphia, Elsevier Saunders, 2006, KaIssI A.A., Ghachem M.B., NecIb M.N., ChehIda F.B., KarouI H., BaraItser M.: Hypohidrotic ectodermal dysplasia with tibial aplasia. Clin. Dysmorphol., 2002, 11(3), Nager F.R., dereynier.: Das Gehororgan bei den angeborenen Kopfmissbildungen. Pract. Otorhinolaryngol., 1948, 10(2), Opıtz J.M., Mollıca F., Sorge G., Mılana G., Cımıno G., Caltabıano M.: Acrofacial dysostoses: review and report of a previously undescribed condition: the autosomal or X-linked dominant Catania form of acrofacial dysostosis. Am. J. Med. Genet., 1993, 47, Thompson E., Cadbury R., BaraItser M.: The Nager acrofacial dysostosis syndrome with the tetralogy of Fallot. J. Med. Genet., 1985, 22, ADDRES FOR CORRESPONDENCE: Ali Karaman, MD Department of Medical Genetics Erzurum Nenehatun Obstetrics and Gynecology Hospital (Erzurum Nenehatun Kadın Doğum Hastanesi) Erzurum, Turkey Tel: ; Fax: alikaramandr@hotmail.com 253

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SWISS SOCIETY OF NEONATOLOGY. Chromosome 13q deletion syndrome

SWISS SOCIETY OF NEONATOLOGY. Chromosome 13q deletion syndrome SWISS SOCIETY OF NEONATOLOGY Chromosome 13q deletion syndrome November 2002 2 Leone A, Pasquier S, Neonatal Intensive Care Unit, Children s Hospital of Aarau, Kinderspital Aarau, Aarau, Switzerland Title