Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3

Clinical Characteristics
Ocular Features: 

Deep-set eyes with highly arched eyebrows have been described and poor fixation can be present.  Cortical visual impairment has been described.

Systemic Features: 

The neurologic abnormalities become evident soon after birth.  Hypotonia and decreased reflexes may be present early and often there is little psychomotor development subsequently.  Some patients have no or very little speech and may never sit, stand, or walk.  However, there is considerable variation in the clinical picture and other individuals are able to walk and may live into the third decade.  Brain imaging reveals a variety of abnormalities including cerebellar and cerebral hypoplasia.  Respiratory difficulties and poor feeding are often present.

The facial dysmorphism may include brachycephaly with a broad forehead and narrowing of the temporal regions.  The nose may be small and the mouth appears large in the presence of micrognathia and a thin upper lip.

Genetics

This is an autosomal recessive condition as the result of homozygous or compound heterozygous mutations in the TBCK gene (4q24). 

Other similar conditions include IHPRF2 (616801) (with homozygous mutations in UNC80 and IHPRF1 (615419) (with homozygous mutations in NALCN) whose ocular features may include strabismus, nystagmus, and poor visual fixation.    

Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia

Bhoj EJ, Li D, Harr M, Edvardson S, Elpeleg O, Chisholm E, Juusola J, Douglas G, Guillen Sacoto MJ, Siquier-Pernet K, Saadi A, Bole-Feysot C, Nitschke P, Narravula A, Walke M, Horner MB, Day-Salvatore DL, Jayakar P, Vergano SA, Tarnopolsky MA, Hegde M, Colleaux L, Crino P, Hakonarson H. Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia. Am J Hum Genet. 2016 Apr 7;98(4):782-8.

PubMed ID: 
27040691

Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy

Chong JX, Caputo V, Phelps IG, Stella L, Worgan L, Dempsey JC, Nguyen A, Leuzzi V, Webster R, Pizzuti A, Marvin CT, Ishak GE, Ardern-Holmes S, Richmond Z; University of Washington Center for Mendelian Genomics, Bamshad MJ, Ortiz-Gonzalez XR, Tartaglia M, Chopra M, Doherty D. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. Am J Hum Genet. 2016 Apr 7;98(4):772-81.

PubMed ID: 
27040692

References

Bhoj EJ, Li D, Harr M, Edvardson S, Elpeleg O, Chisholm E, Juusola J, Douglas G, Guillen Sacoto MJ, Siquier-Pernet K, Saadi A, Bole-Feysot C, Nitschke P, Narravula A, Walke M, Horner MB, Day-Salvatore DL, Jayakar P, Vergano SA, Tarnopolsky MA, Hegde M, Colleaux L, Crino P, Hakonarson H. Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia. Am J Hum Genet. 2016 Apr 7;98(4):782-8.

PubMedID: 27040691

Chong JX, Caputo V, Phelps IG, Stella L, Worgan L, Dempsey JC, Nguyen A, Leuzzi V, Webster R, Pizzuti A, Marvin CT, Ishak GE, Ardern-Holmes S, Richmond Z; University of Washington Center for Mendelian Genomics, Bamshad MJ, Ortiz-Gonzalez XR, Tartaglia M, Chopra M, Doherty D. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. Am J Hum Genet. 2016 Apr 7;98(4):772-81.

PubMedID: 27040692