Congenital-onset Steinert myotonic dystrophy(Congenital-onset Steinert myotonic dystrophy)
Congenital-onset Steinert myotonic dystrophy (SMD), also known as congenital-onset myotonic dystrophy type 1 (DM1), is a severe form of myotonic dystrophy that presents at birth or in early infancy. It is characterized by profound muscle weakness, respiratory issues, and significant developmental delays. This condition is caused by a mutation in the DMPK gene, leading to the expansion of a trinucleotide (CTG) repeat in the gene.
疾病机制
Congenital-onset Steinert myotonic dystrophy (SMD) is caused by an expansion of the CTG trinucleotide repeat in the DMPK gene on chromosome 19. Normally, the DMPK gene contains a repeat of the CTG sequence ranging from 5 to 37 repeats. In individuals with congenital-onset SMD, this repeat is expanded to over 1,000 copies. This expansion leads to the production of toxic RNA molecules that interfere with the normal function of various proteins involved in muscle development and maintenance, resulting in the characteristic symptoms of the disease.
临床表现
- Muscle Weakness: Profound muscle weakness is present at birth or develops shortly after. This includes generalized hypotonia (low muscle tone) and significant difficulty with movement.
- Respiratory Issues: Respiratory muscle weakness can lead to respiratory distress, requiring mechanical ventilation in some cases.
- Developmental Delays: Severe developmental delays are common, including delays in motor skills, speech, and cognitive development.
- Feeding Difficulties: Due to muscle weakness, infants may have difficulty with feeding, leading to poor weight gain and growth.
- Cardiac Involvement: Some patients may have cardiac abnormalities, such as arrhythmias or conduction defects.
- Facial Dysmorphism: Characteristic facial features may include a high forehead, ptosis (drooping eyelids), and a small jaw.
诊断
- Clinical Diagnosis: The diagnosis is primarily based on clinical features, including the presence of muscle weakness, respiratory issues, and developmental delays.
- Genetic Testing: Molecular genetic testing is essential for confirming the diagnosis. This involves detecting the expanded CTG repeat in the DMPK gene.
- Electromyography (EMG): EMG may show characteristic myotonic discharges, which are a hallmark of myotonic dystrophy.
- Muscle Biopsy: In some cases, a muscle biopsy may be performed to observe the characteristic pathological changes associated with the disease.
遗传咨询
- Autosomal Dominant Inheritance: Congenital-onset SMD follows an autosomal dominant inheritance pattern. This means that a single copy of the mutated gene in each cell is sufficient to cause the disorder.
- Prenatal Testing: Prenatal testing, including chorionic villus sampling (CVS) or amniocentesis, can be offered to families at risk if the mutation has been identified in a family member.
- Counseling for Family Planning: Genetic counseling is crucial for families to understand the inheritance pattern, risk of recurrence, and options for family planning.
- Support for Affected Families: Providing emotional and practical support to affected families is an important aspect of genetic counseling.
预后
The prognosis for congenital-onset Steinert myotonic dystrophy is generally poor. Many infants with this condition do not survive beyond early childhood due to severe respiratory complications. For those who survive, life expectancy is reduced, and quality of life is significantly impacted by the severe muscle weakness and developmental delays. Early intervention with multidisciplinary care, including respiratory support, physical therapy, and nutritional support, can improve outcomes, but the condition remains life-threatening and debilitating.