HUT (Hutterite)

Inheritance: autosomal recessive
Genes: FKRP

LGMD2I

Muscular dystrophy
Limb girdle
Calf hypertrophy
Weakness
Cardiac weakness
Creatine kinase deficiency
Kyphoscoliosis
Respiratory insufficiency

Limb-Girdle Muscular Dystrophy, Type 2I

Clinical Characteristics

General description (for patients):

Muscle weakness, especially in the lower limbs, is the early sign in this disease.  Onset often occurs in childhood but becomes pronounced by the 2nd decade.  Easy fatigability and difficulty in climbing stairs are common early signs.  There may be breathing difficulties and cardiac involvement with signs of heart failure as well. Progression may vary but many patients are confined to a wheelchair by the third decade or even earlier.  Physical therapy and a moderate exercise program may be helpful in the early stages while breathing assistance at night can be beneficial.

Medical description:  

This is one of two types of muscular dystrophy found among Hutterites (see also #254110). Generalized weakness especially in the lower extremities may be noted as early as six months but almost always by the second decade.  Progression can result in wheelchair confinement as early as the second decade of life.  Calf hypertrophy and a clinical spectrum resembling Duchenne’s muscular dystrophy are sometimes seen.  Cardiac involvement with abnormal left ventricular motion is seen in this type of LGMD.  Serum creatine kinase is usually elevated.  Spinal curvature abnormalities and respiratory insufficiency are often present.  Severe reactions to general anesthesia may occur.

Genetics:

A mutation (826C>A) in the gene coding the fukutin-related protein (FKRP) causes type 2I muscular dystrophy.  The gene is located on chromosome 19 (9q13.3).  It is an autosomal recessive disorder and has been found in at least five Hutterite families.

Treatment:

Moderate intensity endurance training may improve daily functioning.

Prognosis:

Poor. Progression always occurs and unassisted locomotion becomes impossible by the third and fourth decades or earlier.

Ancillary treatments and support:

General supportive treatment as needed.  A moderate exercise program in the early stages and nocturnal ventilator assistance may be helpful.

Specialists and specialty centers:

Pediatrician, Physical Therapy.

References:

Frosk, P., Del Bigio, M.R., Wrogemann, K., and Greenberg, C.R.:  Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.  Europ. J. Med. Genet. 13: 978-982, 2005.  PubMed ID: 15886712

Frosk, P., Greenberg, C.R., Tennese, A.A.P., Lamont, R., Nylen, E., Hirst, C., Frappier, D., Roslin, N.M., Zaik, M., Bushby, K., Straub, V., Zatz, M. de Paula, F., Morgan K., Fujiwara, T.M., and Wrogemann, K.:  the most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.  Hum. Mutat. 25: 38-44. 2005.  PubMed ID: 15580560

Mercuri, E., Brockington, M., Straub, V., Quijano-Roy, S., Yuva, Y., Herrmann, R., Brown, S.C., Torelli, S., Dubowitz, V., Blake, D.J., Romero, N.B., Estournet, B., Sewry, C.A., Guicheney, P., Voit, T., and Muntoni, F.:  Phenotypic spectrum associated with mutations in the fukutin-related protein gene.  Ann. Neurol. 53: 537-542, 2003.  PubMed ID: 12666124

Resources:

Muscular Dystrophy Association