Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Diagnostic classification and clinical aspects of floppy infants in the neonatal and pediatric intensive care units

신생아 및 소아 중환자실에 입원한 늘어지는 영아(floppy infant)의 진단적 분류 및 임상적 고찰

  • Kim, Eun Sun (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Jung, Kyung Eun (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Sang Duk (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Eo Kyung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Chae, Jong Hee (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Han Suk (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Park, June Dong (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Ki Joong (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Beyong Il (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Hwang, Yong Seung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Choi Jung-Hwan (Department of Pediatrics, Seoul National University College of Medicine)
  • 김은선 (서울대학교 의과대학 소아과학교실) ;
  • 정경은 (서울대학교 의과대학 소아과학교실) ;
  • 김상덕 (서울대학교 의과대학 소아과학교실) ;
  • 김이경 (서울대학교 의과대학 소아과학교실) ;
  • 채종희 (서울대학교 의과대학 소아과학교실) ;
  • 김한석 (서울대학교 의과대학 소아과학교실) ;
  • 박준동 (서울대학교 의과대학 소아과학교실) ;
  • 김기중 (서울대학교 의과대학 소아과학교실) ;
  • 김병일 (서울대학교 의과대학 소아과학교실) ;
  • 황용승 (서울대학교 의과대학 소아과학교실) ;
  • 최중환 (서울대학교 의과대학 소아과학교실)
  • Received : 2006.08.16
  • Accepted : 2006.09.13
  • Published : 2006.11.15
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Abstract

Purpose : The purpose of this study is to make a diagnostic classification and discuss a diagnostic strategy of floppy infants by investigating clinical, neurological, electrophysiological, and genetic analysis of infants admitted to intensive care units with the complaint of hypotonia. Methods : A retrospective study was performed from Jan. 1993 to Dec. 2005 in neonatal and pediatric intensive care units of Seoul National University Children's Hospital. Clinical features and all tests related to hypotonia were investigated. Results : There were 21 cases of floppy infants admitted to intensive care units. Final diagnosis was classified as centra (7 cases[33.3 percent]), peripheral (11 cases [52.4 percent]), and unspecified (3 cases [14.3 percent]). Among the central group, three patients were diagnosed as hypoxic ischemic encephalopathy, two patients as Prader-Willi syndrome, one patient as chromosomal disorder, and one patient as transient hypotonia. Among the peripheral group, four patients were diagnosed as myotubular myopathy, three patients as SMA type 1, two patients as congenital myotonic dystrophy, one patient as congenital muscular dystrophy, and one as unspecified motor-neuron disease. Motor power was above grade 3 on average, and deep tendon reflex was brisk in the central group. Among investigations, electromyography showed 66 percent sensitivity in the peripheral group, and muscle biopsy was all diagnostic in the peripheral group. Brain image was diagnostic in the central group, and Prader-Willi FISH or karyotyping was helpful in diagnosis in central group. Morbidity and mortality was more severe in the peripheral group Conclusion : Classification of diagnosis by clinical characteristics in this study, and application of investigations step by step, may provide an effective diagnostic strategy.

목 적 : 늘어지는 증상을 주소로 신생아 및 소아 중환자실에 입원한 영아들의 임상적, 신경학적, 전기생리학적 소견 및 유전적 진단 결과를 통한 분석을 통해 늘어지는 영아 증후군의 진단적 분류 및 진단 방법에 대한 고찰을 하고자 하였다. 방 법 : 1993년도부터 2005년까지 13년간 서울대학교 병원 어린이병원 신생아 중환자실 및 소아 중환자실에 늘어지는 증상을 주된 주소로 입원한 영아들을 대상으로 하였다. 후향적 의무기록조사를 통해 임상 소견 및 검사 소견들을 조사하였고 최종 진단명을 분류하였다. 결 과 : 늘어지는 증상을 주소로 내원한 영아들은 21명이었다. 최종 진단명은 중추성 기원이 7명(33.3%), 말초성 기원이 11명(52.4%), 나머지 3명은(14.3%) 두 그룹 중 어느 그룹으로도 분류되지 못하였다. 중추성 기원은 저산소-허혈성 뇌증이 3명으로 가장 많았고, 그 외에 Prader-Willi 증후군 2명, 염색체 이상 1명, 일과성 저긴장증 1명이 있었다. 말초성 기원은 myotubular 근병증이 4명으로 가장 많았고, SMA 1형이 3명, 선천성 근긴장성 이영양증 2명, 선천성 근이영양증 1명, 그 외 분류되지 않은 운동신경질환 1명이 있었다. 가족력이 있었던 경우는 말초성 그룹에서만 3명이 있었고, 신경학적 검진 상 근력은 중추성 그룹에서 평균 Grade 3 이상이었고 건반사도 활발하게 나타난 경우가 많아 다른 그룹의 환자들과 차이를 보였다. 검사상의 소견은 근전도 검사에서 말초성 그룹이 66%의 민감도를 보였고 근생검은 말초성 그룹에서 진단적이었다. 중추성 그룹에서 뇌 영상 검사가 진단적이었고 진단율이 높지는 않았지만 Prader-Willi FISH 나 염색체 검사를 통해 진단이 되었던 경우가 있었다. 그외의 분자 유전학적 검사로 확진 가능한 말초성 그룹의 환자들이 있었다. 입원 기간 및 기관 삽관 기간은 말초성 그룹에서 현저하게 길었고, 추적 관찰 시 사망 및 심한 발달 지체의 비율도 말초성 그룹에서 높게 나타났다. 결 론 : 본 연구의 늘어지는 영아들의 임상상을 바탕으로 진단적 분류를 시행하고 각 진단 분류에 유용한 검사를 순서대로 진행시킨다면 효과적인 진단이 이루어질 수 있을 것이다.

Keywords

References

  1. Jebsen RH, Johnson EW, Knobloch H, Grant DK. Differential diagnosis of neonatal hypotonia. Am J Dis Child 1961;101:34-43
  2. Paine RS. The future of the 'floppy infant': a followup study of 133 patients. Dev Med Child Neurol 1963;5:115-24 https://doi.org/10.1111/j.1469-8749.1963.tb05010.x
  3. Richer LP, Shevell MI, Miller SP. Diagnostic profile of neonatal hypotonia: an 11year study. Pediatr Neurol 2002;26:32-7
  4. ParoPanjan D, Neubauer D. Congenital hypotonia: is there an algorithm- J Child Neurol 2004;19:439-42 https://doi.org/10.1177/088307380401900608
  5. Birdi K, Prasad AN, Prasad C, Chodirker B, Chudley AE. The floppy infant: retrospective analysis of clinical experience(1990-2000) in a tertiary care facility. J Child Neurol 2005;20:803-8 https://doi.org/10.1177/08830738050200100401
  6. Dubowitz V. The floppy infant syndrome. In : Dubowitz V, editor. Muscle Disorders in Childhood. 1st ed. Philadelphia:WB Saunders Co, 1978:223-31
  7. Dunn HG, Ford DK, Auersperg N, Miller JR. Benign congenital hypotonia with chromosomal anomaly. Pediatrics 1961;28:578-91
  8. Carboni P, Pisani F, Crescenzi A, Villani C. Congenital hypotonia with favorable outcome. Pediatr Neurol 2002;26:38-36
  9. Shuper A, Weitz R, Varsano I, Mimouni M. Benign congenital hypotonia. A clinical study in 43 children. Eur J Pediatr 1987;146:360-4 https://doi.org/10.1007/BF00444937
  10. Thompson CE. Benign congenital hypotonia is not a diagnosis. Dev Med Child Neurol 2002;44:28-36
  11. Prasad AN, Prasad C. The floppy infant : contribution of genetic and metabolic disorders. Brain Dev 2003;25:457-76 https://doi.org/10.1016/S0387-7604(03)00066-4
  12. Dobyns WB, Pagon RA, Armstrong D, Curry CJ, Greenberg F, Grix A, et al. Diagnostic criteria for Walker-Warburg syndrome. Am J Med Genet 1989;32:195-210 https://doi.org/10.1002/ajmg.1320320213
  13. Dua T, Das M, Kabra M, Bhatia M, Sarkar C, Arora S, et al. Spectrum of floppy children in Indian scenario. Indian Pediatr 2001;38:1236-43
  14. Premasiri MK, Lee YS. The myopathology of floppy and hypotonic infants in Singapore. Pathology 2003;35:409-13 https://doi.org/10.1080/00313020310001602648
  15. Gordon N. Arthrogryposis multiplex congenita. Brain Dev 1998;20:507-11 https://doi.org/10.1016/S0387-7604(98)00037-0
  16. Dubowitz V. A colour atlas of muscle disorders in childhood. 1st ed. London : Wolfe Medical Publications Ltd, 1989:521-33
  17. Denizot S, Boscher C, Le Vaillant C, Roze JC, Gras Le Guen C. Distal arthrogryposis and neonatal hypotonia: an unusual presentation of PraderWilli syndrome (PWS). J Perinatol 2004;24:733-4 https://doi.org/10.1038/sj.jp.7211185
  18. Kang PB, Lidov HG, David WS, Torres A, Anthony DC, Jones HR, et al. Diagnostic value of electromyography and muscle biopsy in arthrogryposis multiplex congenita. Ann Neurol 2003;54:790-5 https://doi.org/10.1002/ana.10769
  19. Koh TH. Do you shake hands with mothers of floppy babies? Br Med J(Clin Res Ed) 1984;289:485 https://doi.org/10.1136/bmj.289.6443.485
  20. Pitt M, Pressler R. Neurophysiological testing in the newborn and infant. Early Hum Dev 2005;81:939-46 https://doi.org/10.1016/j.earlhumdev.2005.10.005
  21. Jones HR Jr. EMG evaluation of the floppy infant: differential diagnosis and technical aspects. Muscle Nerve 1990;13:338-47 https://doi.org/10.1002/mus.880130410
  22. David WS, Jones HR Jr. Electromyography and biopsy correlation with suggested protocol for evaluation of the floppy infant. Muscle Nerve 1994;17:42430
  23. Crawford TO. Clinical evaluation of the floppy infant. Pediatr Ann 1992;21:348-54 https://doi.org/10.3928/0090-4481-19920601-06
  24. Aydinli N, Baslo B, Caliskan M, Ertas M, Ozmen M. Muscle ultrasonography and electromyography correlation for evaluation of floppy infants. Brain Dev 2003;25:22-4 https://doi.org/10.1016/s0387-7604(02)00119-5
  25. Dreesen JC, Bras M, de DieSmulders C, Dumoulin JC, Cobben JM, Evers JL, et al. Preimplantation genetic diagnosis of spinal muscular atrophy. Mol Hum Reprod 1998;4:881-5 https://doi.org/10.1093/molehr/4.9.881
  26. Kesari A, Rennert H, Leonard DG, Mittal B. SMN1 dosage analysis in spinal muscular atrophy from India. BMC Med Genet 2005;6:22 https://doi.org/10.1186/1471-2350-6-22
  27. Tarnopolsky MA, Bourgeois JM, Fu MH, Kataeva G, Shah J, Simon DK, et al. Novel SCO2 mutation(G1521A) presenting as a spinal muscular atrophy type I phenotype. Am J Med Genet A. 2004;1;130A:218
  28. Mancuso M, Salviati L, Sacconi S, Otaequi D, Camano P, Marina A, et al. Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. Neurology 2002;59:1197-202 https://doi.org/10.1212/01.WNL.0000028689.93049.9A
  29. Dubowitz V. Congenital muscular dystrophy: an expanding clinical syndrome. Ann Neurol 2000;47:143-4 https://doi.org/10.1002/1531-8249(200002)47:2<143::AID-ANA2>3.0.CO;2-Y
  30. Swaiman KF, Iannaccone ST. Neuromuscular disorders. In:Swaiman KF, Ashwal S, editors. Pediatric Neurology. 3rd ed. St. Louis : Mosby, Inc. 1999:57;1168,1262
  31. Chae JH, Hwang YS. Neuromuscular disorders in childhood. J Korean Pediatr Soc 2003;46:109-15