Table 2.
Detailed symptoms in the Hh-related disease. ND, not determined.
| Disease name | Symptoms | Major causal genes (Hh-related) | References |
|---|---|---|---|
| skeletal defects | |||
| Holoprosencephaly (HPE) | abnormal brain and facial structure; midfacial clefts such as cleft lip and palate, cyclopia (single eye) | Shh, HHAT, Disp, Cdo, Gas1, Gli2 | Roessler et al., 1997; Heussler et al., 2002; Roessler et al., 2003; Roessler et al., 2009; Kantarci et al., 2010; Bae et al., 2011; Pineda-Alvarez et al., 2012 Dennis et al., 2012; |
| Greig cephalopolysyndactyly syndrome (GCPS) | abnormal development of the limbs, head, and face | Gli3 | Pettigrew et al., 1991; Wild et al., 1997 |
| Brachydactyly | short fingers | Ihh | Byrnes et al., 2009; Gao et al., 2001 |
| acrocapitofemoral dysplasia | short limbs, relatively large head and narrow thorax | Ihh | Hellemans et al., 2003 |
| hereditary multiple exostoses (HME) | reduced skeletal size and multiple, cartilage-capped, accompanied with benign bone tumors (exostoses) | Ext1/2 | Wuyts et al., 1998; Beltrami et al., 2016 |
| Gorlin's syndrome | a high risk of tumorigenesis, especially skin cancer. Also develop noncancerous (benign) tumors of the jaw. | Ptch1 | Fujii et al., 2013 |
| Curry-Jones Syndrome | multisystem disorder; patchy skin lesions, polysyndactyly etc. | Smo (active mutations) | Zhou et al., 2012 |
| Donnai-Barrow syndrome | HPE-like phenotypes | LRP2 | Kantarci et al., 2007 |
| Acrocallosal syndromes | brain abnormality (failure of the corpus callosum development), extra fingers and toes (polydactyly), distinctive facial features. | Kif7 | Putoux et al., 2011 |
| ciliopathies | |||
| Joubert syndrome | eye abnormalities (such as retinal dystrophy), kidney disease, liver disease, extra fingers and toes, | Kif7, SuFu | Aguilar et al., 2012; De Mori et al., 2017 |
| Meckel syndrome | sac-like protrusions (Occipital encephalocele) or no major prtion of the brain (anencephaly), severely cystic kidneys, and abnormal liver and skeleton | Kif7 | Aguilar et al., 2012 |
| tumors, cancers | |||
| medulloblastoma (MB) | neuroectodermal tumor in the cerebellum | Ptch2, SuFu | Rusert et al., 2014; Millard and De Braganca, 2016 |
| basal cell carcinoma (BCC) | skin cancer | Ptch1, Ptch2, SuFu | Schulman et al., 2016 |
| basal cell nevus syndrome (BCNS) | skeletal abnormalities, jaw keratocysts, calcification of brain structures, carcinoma | Ptch1, Ptch2, SuFu | Johnson et al., 1996; Kimonis et al., 1997; Goodrich et al., 1997; De Mori et al., 2017; |
| neurological disorders | |||
| Parkinson’s disease (PD) | motor deficiencies (slowness of movement, tremors, and postural instability) | ND (involvement of Hh signal has been suggested) | Gonzalez-Reyes et al., 2012 |
| Alzheimer’s disease (AD) | deterioration of cognitive and memory functions | ND (involvement of Hh signal has been suggested) | Vorobyeva and Saunders, 2018 |