Presentation: Neonate with suspected myotonic dystrophy type 1

A baby is admitted to the neonatal unit immediately after birth with respiratory distress requiring ventilation. The baby is profoundly hypotonic with poor respiratory effort. Contractures are noted at the knees and ankles and there are reduced anti-gravity movements. Polyhydramnios and reduced fetal movements were noted during pregnancy. Family history reveals that the mother has cataracts and diabetes. On examination, you see that she also has a myopathic face.

• Genomic testing should be considered in the presence of a combination of several of the following features:
  • unexplained respiratory distress;
  • prolonged unexplained ventilatory requirement;
  • significant unexplained feeding difficulties or absent suck and swallow reflexes;
  • severe persistent hypotonia;
  • talipes equinovarus;
  • contractures;
  • polyhydramnios during pregnancy; and
  • suspected or known diagnosis of myotonic dystrophy type 1 in the mother or maternal family.
• A paternal family history of myotonic dystrophy type 1 is not typically expected to cause congenital onset, and other diagnoses should be considered.
• A genetic diagnosis may have implications for other family members, and can be particularly relevant during a pregnancy. For some genetic conditions, rapid testing is available for the purposes of pregnancy management. Assessment of symptoms during pregnancy and discussion of the patient’s choices regarding prenatal testing may be offered. If the patient or a close relative is pregnant, you may wish to offer them a referral to the local clinical genetics service for discussion.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient and/or their family.
  • R72 Myotonic dystrophy type 1. This panel involves short tandem repeat (STR) testing, which is indicated for infants whose clinical features are strongly suggestive of myotonic dystrophy type 1. It looks for STRs in the DMPK gene, and will typically show a large expansion in affected infants. The number of STRs is not typically reported where expansion sizes exceed 150 repeats.
  • R410 Myotonic dystrophy type 2. This panel should not be used in this scenario because myotonic dystrophy type 2 is not expected to present with severe neonatal symptoms.
• If R72 is negative, other diagnoses may be considered in a hypotonic infant, including other neuromuscular conditions that might present in infancy. For more information, see Child acutely unwell in NICU or PICU.
• For tests that do not include whole genome sequencing, including R72, you should use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• The diagnosis of congenital myotonic dystrophy type 1 in a neonate may reveal the same diagnosis in the mother, and an early referral to the local clinical genetics service is advised.
• For alternative diagnoses and tests, parental samples may be needed for interpretation of the proband’s result; parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• R72 is a DNA-based test, and an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• GeneReviews: Myotonic dystrophy type 1
• NHS England: National Genomic Test Directory
• OMIM: #160900 Myotonic dystrophy 1

References:

• Aldana EZ, Angeard N, Johnson NE and others. ‘Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1’. Neurology Clinical Practice 2019: volume 9, issue 5, pages 443–454. DOI: 10.1212/CPJ.0000000000000646
• Barbé L, Lanni S, López-Castel A and others. ‘CpG methylation, a parent-of-origin effect for maternal-biased transmission of congenital muscular dystrophy’. American Journal of Human Genetics 2017: volume 100, issue 3, pages 488–505. DOI: 10.1016/j.ajhg.2017.01.033

For patients

• Myotonic Dystrophy Foundation
• Myotonic Dystrophy Support Group