Mobius Syndrome with Poland's Anomaly*

J Med Genet: first published as 10.1136/jmg.10.2.192 on 1 June 1973. Downloaded from

192 Case Reports this decision was provided to the parents through- out many visits. Mobius Syndrome with Poland's Patients with Down's syndrome may have Anomaly* cryptorchidism or a small penis but other genital developmental abnormalities are uncommon Summary. A five-year-old boy with (Hamerton, 1971). Only one case of pseudoherm- Mobius syndrome, Poland's anomaly, aphroditism in a patient with Down's syndrome and dextrocardia is described. These has been reported previously and that was a female malformations have not been with congenital adrenal hyperplasia (Srivuthana, previously et al, 1971). There is some evidence, however, that reported. The propositus had ipsilateral the association of sex chromosome aneuploidy and absence of the sternal portion of the pec- Down's syndrome is higher than would be statisti- toralis major muscle associated with cally expected (Taylor and Moores, 1967). The acromicria, syndactyly, brachydactyly of lack of reported cases with the association of the the index, middle, ring, and fifth finger, two abnormal states seen in our patient suggests as well as radiological evidence of hypo- their simultaneous occurrence is coincidental. In plasia ofthe index middle and ring fingers, view of the large series of patients with Down's associated with syndactylia and absent syndrome reported we feel that if a common middle phalanges. mechanism for these abnormalities existed more cases of their co-existence would have been reported. Mobius syndrome associated with Poland's Two and a half years after the birth of the patient, anomaly, as represented by the case reported here, her mother became pregnant by her second husband. has not been previously described. Fifteen weeks after her last menstrual period an The first report of congenital bilateral facial par- amniocentesis was performed because of her in- alysis was made by von Graefe in 1880. In 1888, creased risk of bearing another child with Down's Mobius emphasized the nuclear agenesis of the syndrome. The karyotype on the amniotic fluid cranial nerves. Some of the most comprehensive cells was 46,XY. The possibility of this fetus be- reviews of this rare disorder were made by Hender- ing affected if the mother was the carrier of an X- son in 1939, Danis in 1945, Gorlin and Pindborg linked form of male pseudohermaphroditism was in 1964 as well as others (Hellstr6m, 1949; Richards, discussed with the parents. A normal male infant 1953; Evans, 1955). was delivered at term. Alfred Poland in 1841, dissected the body of a criminal with unilateral symbrachydactyly associ- http://jmg.bmj.com/ MITCHELL S. GOLBUS, ated with ipsilateral (same side) aplasia of the sternal CHARLES J. BEAUCHAMP, COL. USAF, head of the pectoralis major muscle. In 1900, and FELIX A. CONTE Furst provided a detailed analysis of the type of hand malformation, the associated muscle defects and insight into the aetiology. Department of Pediatrics University of California- San Francisco; San Francisco, California 94122 and Case Report

the Department of Pediatrics, David Grant USAF on October 1, 2021 by guest. Protected copyright. This 5-year-old boy was first seen at the Orthopaedic Medical Center, Travis Air Force Base, California Hospital, Los Angeles, California in May 1971, be- 94535, USA. cause of multiple congenital abnormalities involving the eye, facial muscles, jaw, teeth, palate, sternum, chest, and REFERENCES hand. The mother's pregnancy was apparently normal. Hamerton, J. L. (1971). Human Cytogenetics: Clinical Cytogenetics, She gained approximately 15-9 kg in weight from an Vol. 2. Academic Press, New York. initial weight of 66&7 kg. The father and mother were Saez, J. M., Fr6d6rich, A., and Bertrand, J. (1971). Endocrine and unrelated, and were both 30 years of age at the time of metabolic studies in children with male pseudohermaphroditism. birth. The was 4 0 The 3'ournal of Clinical Endocrinology, 32, 611-618. the patient's birthweight kg. Srivuthana, S., Collipp, P., Sherman, J., and Zaino, E. (1971). baby breathed and cried spontaneously. No diagnosis of Translocation mongolism with virilizing adrenal hyperplasia. any syndrome was made. He had two operations on his American Journal of Clinical Pathology, 55, 232-236. eye muscles for stabismus, at age 1 and 3 years. There Sumner, A., Evans, H., and Buckland, R. (1971). New technique for distinguishing between human chromosomes. Nature New was no family historyofneurological or somatic disorders. Biology, 232, 31-32. Taylor, A., and Moores, E. (1967). A sex chromatin survey of new- Received 27 November 1972. born children in two London hospitals. Journal of Medical * Address reprint requests to: G.I.S., 3325 Division Street, Los Genetics, 4, 258-259. Angeles, California 90065, USA. J Med Genet: first published as 10.1136/jmg.10.2.192 on 1 June 1973. Downloaded from Case Reports 193 Physical Examination. The 5-year-old boy was plastic mandibles; (8) obesity; (9) short, fixed stemrnum alert, co-operative, normally intelligent, but somewhat with aplasia of the sternal portion of the left pectoralis sensitive about his abnormalities. He had the following major muscle (Figs. 2a and 2b); (10) dextrocardia with- congenital abnormalities: (1) fixed, expressionless facies out murmurs; (11) left-hand acromicria with soft tissue (Fig. la) with inability of the eyes to move on lateral or syndactyly and brachydactyly ofthe second, third, fourth, medial gaze; (2) inability to close the lids completely and fifth fingers (Fig. 3). He also had slight clubbing of (Fig. lb); (3) bilateral facial nerve paralysis with in- the left fingernails and (12) involvement of the cranial ability to smile; (4) microlingua; (5) hypoplasia of the nerves III, IV, V, VI, VII, IX, and XII. teeth; (6) high arched palate; (7) micrognathia and hypo- His vision, hearing, and sense of smell were intact. He

Fig. la Fig. lb

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Fig. 3

FIG. la. Facies. Note the absence of expression due to facial diplegia (cranial nerve VII). FIG. lb. Facies. Note the difficulty in closing eyelids.

FIG. 2a. Full view. Note hypoplasia of the left pectoralis major muscle and strabismus. FIG. 2b. Full view. Note left hypoplasia of the pectoralis major muscle.

FIG. 3. Hands. Left acromicria, syndactyly, and brachydactyly Fig. 2a Fig. 2b of middle, ring, and little fingers with shortening of the metacarpals. J Med Genet: first published as 10.1136/jmg.10.2.192 on 1 June 1973. Downloaded from 194 Case Reports weighed 23-4 kg was 106-6 cm tall with a head circum- Skull Series. Cranial vault was of average size. ference of 53-3 cm and a chest circumference of 60-3 cm. The sutures were open and were not spread. The The sternocleidomastoid and trapezius muscles were sella turica had normal appearance. There were normal. He had no physical signs of situs inversus or no abnormal intracranial calcifications. The man- congenital heart disorder. The genitalia were normal. dibular angles were quite obtuse. Radiographic Study (2 October 1972) Left hand: AP, Lateral, and Oblique Views. Chest: PA and Lateral Views. The Anatomy of the carpal ossification centres in the dis- heart was prominent in the right chest and was tal radius and ulna was unremarkable. There were rotated to the right (Fig. 4). The aortic arch five metacarpals with finger metacarpals approxi- appeared on the left. Soft tissues of the left mately the same length. There was less than the chest were much thinner than those on the right. usual amount of modelling of the index and middle metacarpals. An accessory ossification centre was present at the base of the second metacarpal and at the distal end of the first metacarpal which also showed lack of normal modelling. The thumb had two phalanges, the proximal thumb phalanx showed an accessory ossification at the distal end. The index, middle, and ring fingers had only two phalanges, the proximal phalanges being slender and the other phalanges quite hypoplastic (Fig. 5). There was syndactylia of these three fingers and together they present a short projecting stump in the middle of the hand. The little finger had three phalanges, although the space between the middle phalanx and the distal phalanx was quite small and may eventually coalesce. http://jmg.bmj.com/ on October 1, 2021 by guest. Protected copyright.

FIG. 4. Radiograph of the chest revealing dextrocardia and de- creased soft tissue of the left side of chest consistent with absence of muscle mass; also short fused sternum.

Pulmonary vasculature was within normal limits and the lungs were clear. The right ribs laterally were a little closer together than the left. There was mild scoliosis. The liver was identifiable on the right with stomach gas bubble present on the left. The sternum was quite short and the seg- ments were fused, including the manubrium. There FIG. 5. Radiograph of the left hand. Note phalangeal absence of the distal second to fourth rays and interphalangeal webbing with was anterior convexity of the sternum just below the hypoplasia most marked in the index, middle, and ring fingers with junction with manubrium. syndactylia, missing middle phalanges and variations of modelling. J Med Genet: first published as 10.1136/jmg.10.2.192 on 1 June 1973. Downloaded from Case Reports 195 Discussion Jorgenson (1971) reported a patient with Mobius Our patient had typical features of Mobius syn- syndrome associated with bilateral hand defects and drome (Table I) as well as Poland's anomaly (Table hypoplasia of the right pectoral muscles. All the II), an unusual association and heretofore unre- fingers of the right hand were missing at the meta- ported. In addition, dextrocardia has not been carpophalangeal joints except for the thumb which previously reported in either Mobius syndrome or was slightly hypoplastic (ectrodactyly). The left Poland's anomaly. Mobius syndrome has been re- hand had a normal thumb and forefinger but the ported with arthrogryposis multiplex congenita, other three digits were hypoplastic with interdigital Klippel-Feil syndrome (Evans, 1955) and fascio- webbing. In contrast, our patient with Mobius scapulohumeral muscular dystrophy (Hanson and syndrome had ipsilateral absence of the sternal por- Rowland, 1971). tion of the pectoralis major muscle associated with acromicria, syndactyly, brachydactyly of the index, TABLE I middle, ring, and fifth digits as well as radiological evidence of hypoplasia of the left index, middle, MOBIUS SYNDROME and ring fingers with syndactylia, absent middle Congenital facial diplegia phalanges, and variations of modelling. (Cranial nerve VII) Additional associated malformations occurring Difficulty in swallowing with Mobius and Poland's anomaly have been sum- (Cranial nerves IX and X) marized in Table I and Table II. Various isolated External ophthalmoplegia sporadic malformations have also been reported: (Cranial nerves VI) unilateral symbrachydactyly, bilateral aplasia of the Other cranial nerves VII, III, and V sternal head of the pectoralis major muscle, and Associated abnormalities bilateral ectrodactyly with a unilateral pectoral 1. Clubfoot 2. Epicanthal folds muscle defect (Ehrenhaft, Rossi, and Lawrence, 3. Hypertelorism 4. Strabismus 1966). 5. Ear abnormalities 6. Micrognathia 7. Bifid uvula We would like to thank Dr R. R. Schreiber, Chief of 8. Palatal palsy Radiology at Orthopaedic Hospital, Los Angeles, Cali- 9. Perodactyly, syndactyly, brachydactyly fornia for the radiographic and 10. Congenital heart disease interpretation Alfred 11. Pectoral muscle hypoplasia Benjamin, RBP, ARPS, Director, Audio-Visual Depart- ment, Orthopaedic Hospital, Los Angeles, California, for the photographs.

TABLE II GERALD I. SUGARMAN and HERBERT H. STARK http://jmg.bmj.com/ POLAND'S ANOMALY AND ASSOCIATED FINDINGS

I. Muscle Metabolic Bone Dysplasia and Genetic Clinic and a. Absence or hypoplasia of pectoralis major (sternal head) USC Hand Clinic, Orthopaedic Hospital, b. Absence or hypoplasia of pectoralis minor c. Absence or hypoplasia of external abdominal, latissimus dorsi, Los Angeles, California, USA serratus anterior, intercostal II. Skeletal a. Syndactyly-brachydactyly REFERENCES b. or Absence hypoplasia of rib on October 1, 2021 by guest. Protected copyright. c. Hemivertebra Danis, P. (1945). Les paralysies oculo-faciales congenitales. d. Absence or hypoplasia ofradius, ulna, carpal, metacarpal, phalange Ophthalmologica, 110, 113. e. Finger webbing Ehrenhaft, J. L., Rossi, N. P., and Lawrence, M. S. (1966). De- f. Sprengel's deformity velopmental chest wall defects. Annals of Thoracic Surgery, 2, III. Skin 384-398. a. Cafe-au-lait pigmentation Evans, P. R. (1955). Nuclear agenesis. Mobius' syndrome. b. Absence of nipples Archives of Disease in Childhood, 30, 237-243. c. Webbing of axilla Furst, C. M. (1900). Ein Fall von verkurzten und zweigliedrigen d. Absence of subcutaneous tissue Fingern, begleitet von Brustmuskeldefecten und anderen Miss- IV. Genitourinary bildungen. Zeitschrift fur Morphologie und Anthropologie, 2, 56- a. Renal aplasia or hypoplasia (Temtamy and McKusick, 1969; 76. Mace et al, 1972) Gorlin, R. J. and Pindborg, J. J. (1964). Syndromes of the Head and b. Pyelonephritis (Temtamy and McKusick, 1969) Neck. McGraw-Hill, New York. c. Undescended testes Graefe, A. von (1880). In Handbuch dergesammten Augenheilkunde, von and T. V. Others ed. by A. Graefe Saemisch, 6, ch. 11. W. Englemann, a. Herniation of lung (Ehrenhaft et al, 1966) Leipzig. b. Acute lymphoblastic leukaemia (Mace et al, 1972) Hanson, P. A. and Rowland, L. P. (1971). Mobius syndrome and c. Absence of the breast or asymmetry facioscapulohumeral muscular dystrophy. Archives of Neuro- d. Hemifacial atrophy logy, 24, 31-39. e. Dextrocardia (not previously reported) Hellstrom, B. (1949). Congenital facial diplegia. Acta Paediatrica, 37, 464-473. J Med Genet: first published as 10.1136/jmg.10.2.192 on 1 June 1973. Downloaded from 196 Case Reports Henderson, J. L. (1939). The congenital facial diplegia syndrome. Brain, 62, 381-403. Jorgenson, R. J. (1971). Mobius syndrome, ectrodactyly, hypoplasia of tongue and pectoral muscles. In The Third Conference on Clinical Delineation of Birth Defects, pt. 11, pp. 283-284. The National Foundation-March of Dimes, New York. Mace, J. W., Kaplan, J. M., Schanberger, J. E., and Gotlin, R. W. (1972). Poland's syndrome. Report of seven cases and review of literature. Clinical Pediatrics, 11, 98-102. Mobius, P. J. (1888). OYber angeborenene doppelsetige Abducens- Facialis-Liihmung. Munchener Medizinische Wochenschrift, 35, 91-94. Poland, A. (1841). Deficiency of the pectorial muscles. Guy's Hospital Reports, 6, 191-193. Richards, R. N. (1953). The Mobius syndrome. Journal of Bone andJoint Surgery, 35A, 637-644. Takeda, M., Suda, Y., Komatsu, S., and Wada, J. (1967). Surgical treatment of congenital chest wall defects associated with congenital deformity of hand. japanese journal of Thoracic Surgery, 20, 559-562. Temtamy, S. and McKusick, V. (1969). Synopsis of hand malformation with particular emphasis on genetic factors. In Birth Defects: Original Article Series, 5, pt. 3, 125-184. The National Foundation-March of Dimes, New York. FIG. 1. Profile of the proposita revealing 'bird-headed' facies, lobeless ears, micrognathia, and pro-optosis.

Familial Bird-headed Dwarfism (Seckel's Syndrome) Summary. Low birth weight dwarfism with mental retardation, large eyes, a beaklike nose, narrow face, receding mandible, and dental anomalies are the specific features of 'bird-headed dwarf of Seckel'. The following case report pre- sents details of a Seckel dwarf with http://jmg.bmj.com/ familial occurrence of the trait and, thus supports an autosomal recessive mode of inheritance. In addition, the possible significance of dental alterations is FIG. 2. Intra-oral view revealing posterior cleft palate and hypo- noted. plastic enamel defects of the primary dentition. The changes on the central incisor have been clinically modified for a restoration.

Case Report on October 1, 2021 by guest. Protected copyright. The proposita is a 46-month-old negro who possessed altered morphology and appeared to be radiographically the clinical syndrome of Seckel's bird-headed dwarfism; normal with regard to morphology, location, and se- the familial occurrence of the trait in three sibs is also quence of development. A hyperostotic ridge could be included. palpated along the sagittal sinus. The head was 30 cm The patient was born 2 May 1969 in Osceola, Arkansas. in circumference. The child weighed 1308 g at birth and 40 weeks' gesta- Hip abduction was almost impossible and the ex- tion. To date the patient presented as severely retarded, tremities revealed scissoring and deep tendon reflexes and weighing 4578 g. with hyperactivity. The radiological examination noted The proposita had microcephaly and oxycephaly, with congenital dislocation of the right hip, thinness of all pro-optosis of the eyes, nystagmus, and lobeless ears long bones, and scoliosis of the thoracolumbar spine. (Fig. 1). Marked micrognathia was noted as was a The skin was free of rashes or petechiae. The nose central posterior cleft of the palate (Fig. 2). The denti- and throat were clear and benign except for a midline tion revealed severe hypoplasia of enamel in the primary posterior cleft of the hard palate. The thyroid was not dentition; however primary second molars showed no enlarged. The chest was symmetrical and shield- shaped with a measurement of 28 cm. Received 15 January 1973. The heart was not enlarged and showed regular sinus