APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: TNNT1

Nemaline myopathy 5
ANM
NEM5
Amish nemaline myopathy

Tremors
Muscle weakness
Contractures
Myopathy
Respiratory insufficiency
Pectus carinatum

Nemaline Myopathy 5 (Amish Type)

Clinical Characteristics

General description (for patients):   

Amish nemaline myopathy presents in the newborn period with tremors, especially in muscles of the jaw and lower limbs.  The name comes from the rodlike (nemaline) bodies seen under the microscope in muscle fibers.  Muscle weakness and contractures can be present early and are progressive.  Motor development is delayed and may be limited to rolling from side-to-side. The chest wall becomes restricted in movement causing severe, often fatal breathing problems in the second year of life.

Medical description:  

All neonates born with ANM exhibit tremors at birth or a few days later involving most skeletal muscle groups but especially those of the jaw and lower limbs. These may subside over several months. However proximal contractures that appear mild at birth gradually worsen with advancing age, such that hip abduction can be restricted to 10° or less by 12 months. Progressive muscle atrophy and weakness develop simultaneously with the contractures.  Gross motor development may be restricted to rolling from side to side. Intelligence seems to be normal.  Severe pectus carinatum deformity with chest wall rigidity is often seen. Muscle biopsies under light microscopy show prominent type 1 fiber disproportion, Z-band streaming, abundant centrally placed refractile rods, and areas of myofibrillar disruption and myofiber degeneration. Diagnosis is based on clinical findings, and the observation of characteristic eosinophilic rod-shaped structures (nemaline bodies) in muscle biopsies.

Genetics:

This autosomal recessive condition is believed to be secondary to a mutation in the TNNT1 gene located on chromosome 19 (19q13.4).  This gene encodes slow skeletal muscle troponin T (TNNT1).  So far it has only been reported in the Lancaster County Amish community. The Amish subtype is caused by a nonsense mutation (579G>T) in this gene resulting in premature truncation of the troponin T protein, thereby removing an essential site of interaction with other components of the troponin complex required for normal muscle contraction.

Treatment:

No treatment is available for the primary disease.

Prognosis:

Death commonly results from respiratory insufficiency in the second year of life.

Ancillary treatments and support:

Monitoring of nutritional status, special feeding techniques, aggressive treatment of lower respiratory tract infections, ventilator use, and standard care for gastroesophageal reflux. Surveillance includes routine assessment for scoliosis, joint contractures, respiratory function, and the need for assistive devices.

Specialists and specialty centers:

Nutritionists, physical and speech therapy.

References:

Johnston, J.J., Kelley, R.I., Crawford, T.O., Morton, D.H., Agarwala, R., Koch, T., Shaffer, A.A., Francomano, C.A., and Biesecker, I.G.:  A novel nemaline myopathy in the Amish caused by a mutation in troponin T1.  Am. J. Hum. Genet.67: 814-821, 2000. PubMed ID: 10952871

Resources:

Nemaline Myopathy Support Group

Associated Graphics