Case 21:

History - A 38 week male neonate was delivered by LSCS for fetal bradycardia. He was found flaccid, cyanotic, apnoeic and required intubation at 1 min of life. A/N history showed intrauterine growth retardation, paucity of fetal movement and polyhydramnios. The baby was kept intubated from day 0 to day 23. After extubation, the baby was noticed to have poor breathing effort requiring nasal SIMV, nasal CPAP and subsequently BiPAP. He was noted to have poor feeding. Family history was unremarkable with no neurological and neuromuscular diseases. Multiple members in the maternal family are affected by cataract.

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Pedigree

Examination of the neurological system is shown in the video clip.

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Video - baby

Q1 - What is the problem?

Answer to Q1

Hypotonia/Floppy Baby Syndrome

Click photos to view
Signs
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 Frog likeposture
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 Head lag on arm traction
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 Inverted U sign in ventral suspension test
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 Slip-through-shoulder sign in vertical suspension test
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 Scarf sign. Note:elbow crossed mid-line
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 Heel-to-ear sign


Q2 -What do you observe on the face of this patient?Compare to the photo of another patient with the same disease (found in textbook).

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Photo1 Photo2

Answer to Q2

Myopathic face

Q3 - What additional feature do you observe in this photo?

Answer to Q3

Undescended testes

 

Q4 - What is the general approach to hypotonia?

Answer to Q4

Please click to open: Approach to Floppy Infant

Further reading:

 


Mother asked to open and clench hands repetitively as quickly as possible

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Video - mother
(She was asked to open and clench hands repetitively as quickly as possible)		 Mother asked to smile Mother asked to blow her cheek

Part of the investigation results of the child:-

CPK: normal

Karyotype 46 XY

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Muscle biopsy report

EMG of patient and his mother

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EMG of Patient EMG of Mother



Q5 -What is the EMG finding for mother and baby?

Answer to Q5

Myotonic discharges

Q6 - What is your diagnosis?

Answer to Q6

Myotonic dystrophy

Comment

The mother also has mild myopathic face with temporal and masseteric wasting. She shows delayed relaxation after clenching, suspicious of myotonia. EMG has been arranged for the mother for confirmation. A normal karyotype excludes syndromic disorder due to chromosomal aberrations. CPK is markedly raised in chronic myopathies such as Duchene muscular dystrophy, dermatomyositis and polymyositis. It is normal to mildly raised in congenital myopathies and myotonic dystrophy.

EMG has not been done in this case but could be helpful. Typical myopathic pattern and denervation pattern should point to different anatomical localization of pathology. Typical pattern may be observed in specific diseases such as myotonia, i.e. trains of spontaneous discharge from single fibre or group of fibres upon stimulation by needle probe, also known as 'dive bomber' pattern when connected to speaker.

Muscle biopsy has been performed in this case. In the workup of floppy infant syndrome, glycogen and lipid storage disease may be demonstrated by presence of storage within muscle fibres. Mitochondrial DNA defect is characterized by ragged red fibres. Several congenital myopathies may show characteristic features such as centrally located nucleus or aggregation of material/enzyme, while some rare forms require electron microscopy or special enzyme staining. Type I fibre hypotrophy is non-specific and can be secondary to a number of causes. (Dunn, D.W. 1987, eMedicine accessed 15/6/2007).

In this patient, genetic test for myotonic dystrophy has been performed and the report shows: -

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Genetic report Southern blot result for our patient

Genetic mechanism of myotonia dystrophica (see separate word file)

Q7 - The mother also provided a family photo. Who do you think is affected?

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Family

Answer to Q7

Mother is the 1st one at the right side. The maternal uncle (2nd one to the left) resembles the mother and is suspected to be affected. Actually all maternal family member, especially those with cataract, need detailed evaluation for myotonic dystrophy. Genetic counseling should be provided if necessary.

Another clinical quiz for hypotonia is available, click here to attempt


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Reference

  1. Wong V. 2007. 'A child with developmental delay' lecture notes. HKU MBBS3.
  2. Dunn, D.W., Epstein L.G.. 1987. Decision Making in Child Neurology. B.C. Decker Inc.. Toronto.
  3. Menkes J.H.. 1985. Textbook of Child Neurology (Third Edition). Lea & Febiger. Philadelphia.
  4. Avery M.E., First L.R.. 1994. Pediatric Medicine Second Edition. Williams & Wikins. Baltimore.
  5. http://www.emedicine.com/neuro/topic76.htm accessed 15/6/2007
  6. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=160900 accessed 24/6/2007
  7. Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barcel? J, O'Hoy K, et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6; 255(5049):1253-5.
  8. Lavedan C., Radvanyi H.H., Shelbourne P., Rabes J.P., Duros C., Savoy D., Dehaupas I., Luce P.S., Johnson K., Junien C.. Myotonic Dystrophy: Size- and Sex-dependent Dynamics of CTG Meiotic Instability, and Somatic Mosaicism. Am. J. Hum. Genet. 52:875-883, 1993.
  9. Jansen G, Willems P, Coerwinkel M, Nillesen W, Smeets H, Vits L, H?weler C, Brunner H, Wieringa B.. Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J Hum Genet. 1994 Apr;54(4):575-85.
  10. John P. Jakupciak and Robert D. Wells. Genetic Instabilities of Triplet Repeat Sequences by Recombination. IUBMB Life, 50: 355-359, 2000.
  11. Ebralidze A., Wang Y., Petkova V., Ebralidse K., Junghans R.P.. RNA leaching of transcription factors disrupts transcription in myotonic dystrophy. Science. 2004 Jan 16;303(5656):383-7. Epub 2003 Dec 4.
  12. de Le?n MB, Cisneros B.. Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanisms. J Neurosci Res. 2007 Jun 4; [Epub ahead of print]
  13. Otten A.D., Tapscott S.J.. Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5465-9.
  14. Peter S. Harper, Helen G. Harley, William Reardon, Duncan J. Shaw. Anticipation in Myotonic Dystrophy: New Light on an Old Problem. Am. J. Hum. Genet. 51:10-16, 1992.
  15. Ashizawa T, Anvret M, Baiget M, Barcel? JM, Brunner H, Cobo AM, Dallapiccola B, Fenwick RG, Grandell U, Harley H, et al. Characteristics of intergenerational contractions of the CTG repeat in myotonic dystrophy. Am J Hum Genet. 1994 Mar;54(3):414-23.

Suggested Reading:

  1. Dunn, D.W., Epstein L.G.. 1987. Decision Making in Child Neurology. B.C. Decker Inc.. Toronto.
  2. Menkes J.H.. 1985. Textbook of Child Neurology (Third Edition). Lea & Febiger. Philadelphia.
  3. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=160900 accessed 24/6/2007

For comments and questions, please send email to: Dr. Brian Chung (bhychung@hkucc.hku.hk)

Dr. Brian Chung, Dr WL Yang, and Wong Wui Bun and Zhu Yi Dan (2007 SSM student)

Acknowledgement: Special Thanks to

Dr P Lee and 2007 SSM "Clinical Genetic" Teaching Group

Dr Sophelia Chan for the EMG clips

Prof V Wong, Dr CW Fung and Neurology Team

Department of Paediatrics & Adolescent Medicine;
The University of Hong Kong