From the Guidelines
The difference in presentations between a mother with mild muscle weakness and lack of facial expression and her neonate with profound hypotonia is most likely due to congenital myotonic dystrophy (myotonic dystrophy type 1), which shows anticipation, meaning symptoms worsen in successive generations due to expansion of CTG trinucleotide repeats in the DMPK gene. This genetic disorder is characterized by a range of symptoms, including muscle weakness, hypotonia, and respiratory difficulties, which are more severe in the congenital form than in the adult-onset form. The mother likely has adult-onset myotonic dystrophy with milder symptoms, while the baby has the more severe congenital form.
Key Features of Congenital Myotonic Dystrophy
- Inherited from the mother and undergoes further expansion during maternal transmission, resulting in earlier onset and more severe symptoms in the child
- Neonate's profound hypotonia reflects this increased genetic severity, manifesting as significant muscle weakness, respiratory difficulties, feeding problems, and potentially facial weakness with an inverted V-shaped upper lip
- Requires immediate multidisciplinary management including respiratory support, feeding assistance, and careful monitoring
- Molecular mechanism involves toxic RNA that disrupts normal cellular function, with greater disruption occurring in the neonate due to the larger number of repeats, explaining the dramatic difference in clinical presentation between mother and child 1.
Differential Diagnosis
Other conditions, such as Prader-Willi syndrome, can also present with hypotonia and feeding problems in infancy, but the combination of maternal muscle weakness and lack of facial expression, along with the neonate's profound hypotonia, makes congenital myotonic dystrophy a more likely diagnosis. Prader-Willi syndrome is characterized by significant cognitive, neurologic, endocrine, and behavioral abnormalities, and is caused by lack of expression of genes from an imprinted region of the paternally inherited chromosome 15q11-q13 1. However, the clinical presentation and genetic mechanism of Prader-Willi syndrome are distinct from those of congenital myotonic dystrophy.
From the Research
Difference in Presentations
The difference in presentations between the mother with mild muscle weakness and lack of facial expression and her neonate with profound hypotonia can be attributed to several factors:
- The mother's condition is likely myasthenia gravis, an autoimmune disorder caused by antibodies against elements in the postsynaptic membrane at the neuromuscular junction, which leads to muscle weakness 2.
- The neonate's condition, on the other hand, could be transient neonatal myasthenia gravis, a temporary condition that occurs in 10-15% of children born to myasthenic mothers 3.
- The transfer of antibodies from the mother to the child during pregnancy can cause the child's condition, but the severity and presentation can vary due to factors such as the level of antibody transfer and the child's individual response 4.
- Another possibility is that the child has a congenital myasthenic syndrome, a rare genetic disorder that affects the neuromuscular junction and can cause muscle weakness and other symptoms 5.
Possible Explanations
Some possible explanations for the difference in presentations include:
- The level of antibody transfer from the mother to the child during pregnancy, which can affect the severity of the child's condition 4.
- The presence of other underlying conditions or factors that can contribute to the child's symptoms, such as genetic mutations or other autoimmune disorders 5.
- The age of onset and the natural history of the condition, which can vary between individuals and affect the presentation and severity of symptoms 2.
- The response to treatment, which can also vary between individuals and affect the presentation and severity of symptoms 6.