Muscular Dystrophy, Congenital, with Cataracts and Intellectual Disability

Clinical Characteristics

Ocular Features:

Cataracts have been diagnosed by 6 months of age and may be congenital in origin. Several patients have had strabismus.

Systemic Features:

Progressive muscle weakness begins in early childhood. Hypotonia is usually present at birth followed by atrophy of the proximal muscles (especially in the lower limbs). Muscle weakness progresses for several years and may stabilize but not before severe gait difficulties occur. Most adult patients are confined to a wheelchair. No cardiac involvement occurs although respiratory weakness is often present. Serum creatine kinase is usually elevated and biopsied muscle fibers show dystrophic changes and increased variability in fiber size with vacuolization.

Other signs in some individuals are contractures, scoliosis, seizures, short stature, cognitive deficits (usually mild), and spinal rigidity. Paradoxically, some patients have limb spasticity and hyperreflexia with pyramidal signs. No cerebellar signs are present.

Genetics

This condition results from homozygous or compound heterozygous mutations in the INPP5K [1] gene (17p13).

See Marinesco-Sjogren Syndrome [2] for a disorder with a somewhat similar clinical presentation plus cerebellar signs. It is caused by a different mutation, however.

Treatment

Treatment Options:

Cataracts have been surgically removed in several patients by the age of two years. Physical therapy may be beneficial. Selected individuals could benefit from release of contractures.

References

Article Title:

INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family [3]

Yousaf S, Sheikh SA, Riazuddin S, Waryah AM, Ahmed ZM. INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family. Clin Genet. 2017 Sep 22. doi: 10.1111/cge.13143. [Epub ahead of print].

PubMed ID:

28940338

Mutations in INPP5K, Encoding a Phosphoinositide 5-Phosphatase, Cause Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment [4]

Wiessner M, Roos A, Munn CJ, Viswanathan R, Whyte T, Cox D, Schoser B, Sewry C, Roper H, Phadke R, Marini Bettolo C, Barresi R, Charlton R, Bonnemann CG, Abath Neto O, Reed UC, Zanoteli E, Araujo Martins Moreno C, Ertl-Wagner B, Stucka R, De Goede C, Borges da Silva T, Hathazi D, Dell'Aica M, Zahedi RP, Thiele S, Muller J, Kingston H, Muller S, Curtis E, Walter MC, Strom TM, Straub V, Bushby K, Muntoni F, Swan LE, Lochmuller H, Senderek J. Mutations in INPP5K, Encoding a Phosphoinositide 5-Phosphatase, Cause Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment. Am J Hum Genet. 2017 Mar 2;100(3):523-536.

PubMed ID:

28190456

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy [5]

Osborn DP, Pond HL, Mazaheri N, Dejardin J, Munn CJ, Mushref K, Cauley ES, Moroni I, Pasanisi MB, Sellars EA, Hill RS, Partlow JN, Willaert RK, Bharj J, Malamiri RA, Galehdari H, Shariati G, Maroofian R, Mora M, Swan LE, Voit T, Conti FJ, Jamshidi Y, Manzini MC. Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjogren Syndrome and Dystroglycanopathy. Am J Hum Genet. 2017 Mar 2;100(3):537-545.

PubMed ID:

28190459