Pontocerebellar Hypoplasia 7

Clinical Characteristics
Ocular Features: 

The ocular phenotype has not been fully evaluated.  Optic atrophy, nystagmus, and strabismus have been reported in addition to dysmorphic periocular features such as epicanthal folds, upslanting lid fissures, and a flattened nasal bridge.  Infants frequently do not fix and follow.

Systemic Features: 

Infants may be small at birth and subsequent psychomotor development is delayed.  The ears are large and the palate is highly arched.  Hypotonia is present from birth but spasticity with hyperreflexia may also be seen.  Brain imaging may show a thin corpus callosum as well as olivopontocerebellar hypoplasia.  The ventricles are frequently enlarged.  Patients are frequently irritable with few spontaneous movements.

Genitalia can be ambiguous and are frequently assigned to the female gender because of microphallus, fused scrotum, absent testes, and absence of the uterus.  Many such infants are found to have XY karyotypes.  Infants considered male at birth may subsequently show regression of penile corporeal tissue and may have genitalia that more closely resemble the female gender.  Pelvic imaging and laparoscopy, however, may reveal a uterus, Fallopian tubes and a blind-ending vagina with no gonadal tissue even in individuals with XY karyotypes. 


Homozygous or compound heterozygous mutations in the TOE1 gene (1p34.1) are responsible for this condition.

Autosomal recessive
Treatment Options: 

No treatment has been reported.

Article Title: 

Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing

Lardelli RM, Schaffer AE, Eggens VR, Zaki MS, Grainger S, Sathe S, Van Nostrand EL, Schlachetzki Z, Rosti B, Akizu N, Scott E, Silhavy JL, Heckman LD, Rosti RO, Dikoglu E, Gregor A, Guemez-Gamboa A, Musaev D, Mande R, Widjaja A, Shaw TL, Markmiller S, Marin-Valencia I, Davies JH, de Meirleir L, Kayserili H, Altunoglu U, Freckmann ML, Warwick L, Chitayat D, Blaser S, Caglayan AO, Bilguvar K, Per H, Fagerberg C, Christesen HT, Kibaek M, Aldinger KA, Manchester D, Matsumoto N, Muramatsu K, Saitsu H, Shiina M, Ogata K, Foulds N, Dobyns WB, Chi NC, Traver D, Spaccini L, Bova SM, Gabriel SB, Gunel M, Valente EM, Nassogne MC, Bennett EJ, Yeo GW, Baas F, Lykke-Andersen J, Gleeson JG. Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing. Nat Genet. 2017 Mar;49(3):457-464.

PubMed ID: 
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