Table 1.
Genes Implicated in Cases of CPHD Can Present With Other Clinical Phenotypes
| Gene | Phenotypesa |
||||
|---|---|---|---|---|---|
| Craniofacialb | Pituitaryc | Peripheral Tissuesd | |||
| ARNT2 | Brain, eye | CPHD | Kidney, urinary tract | ||
| BMP4 | Eye, craniofacial, cleft lip, palate, spina bifida aperta | CPHD | Renal hypodysplasia, hypospadias, polydactyly | ||
| CDON | HPE | (CPHD) | None | ||
| CHD7 | Eye, craniofacial | CPHD | None | ||
| FGF8 | SOD, KS: anosmia | HHe | CPHD | IGHD | Vacterl, hypospadia |
| FGFR1 | Pfeiffer, Hartsfield, Jackson-Weiss syndromes | CPHD | None | ||
| GLI2 | HPE, cleft lip, palate | HH | CPHD | IGHD | Polydactyly, cryptorchidism |
| GLI3 | Pallister Hall syndrome, hypothalamic hamartoma, Greig cephalopolysyndactyly | CPHD | IGHD | Skeletal, polydactyly | |
| GPR161 | None | (CPHD) | (IGHD) | None | |
| HESX1 | SOD | CPHD | IGHD | None | |
| HHIP | HPE | (CPHD) | None | ||
| HNRNPU | Lennox-Gastaut syndrome, CNS, epilepsy, intellectual disability | (CPHD) | None | ||
| IGSF1 | None | CPHD, TSH only | Macro-orchidism | ||
| LHX3 | Hearing | CPHD | Skeletal | ||
| LHX4 | None | CPHD | None | ||
| OTX2 | Eye, craniofacial | CPHD | IGHD | None | |
| PAX6 | Eye | CPHD | None | ||
| PNPLA6 | Spastic paraplegia, Leber congenital amaurosis and other syndromes, eye, craniofacial | HH | CPHD | Muscle wasting | |
| POLR3A | Hypomyelination, hypodontia | HH | (IGHD) | None | |
| POU1F1 | None | CPHD | IGHD | None | |
| PROKR2 | KS: anosmia | HH | (CPHD) | (IGHD) | Hirschsprung disease |
| PROP1 | None | CPHD | None | ||
| RBM28 | Alopecia, neurological defects, intellectual disability, tooth defects | (CPHD) | None | ||
| SHH | HPE, eye, dental anomalies | (CPHD) | None | ||
| SOX2 | Eye, dental anomalies, hearing impairment | HH | CPHD | Micropenis | |
| SOX3 | Intellectual disability, abnormal facial features, speech difficulties, retrognathia, hearing impairment | HH | CPHD | IGHD | Sex reversal, digital anomalies, micropenis |
| TCF7L1 | SOD | CPHD | None | ||
| TGIF1 | HPE | CPHD | None | ||
| WDR11 | Cleft palate, hearing, brain and dental abnormalities, KS: anosmia | HH | (CPHD) | None | |
| ZSWIM6 | Acromelic frontonasal dysostosis, brain | CPHD | Skeletal, cryptorchidism | ||
Phenotypes listed represent the range of symptoms reported in various individuals. The pituitary hormone deficiency and associated craniofacial and peripheral tissue phenotypes can vary and/or be absent.
Craniofacial refers to all aspects of head development except the pituitary, which is listed separately.
The parentheses indicate need for additional evidence or patient examples to add certainty to the role of the gene with the indicated pituitary phenotype.
Peripheral tissue phenotypes are listed, except for those that are secondary to the pituitary hormone deficiencies.
The HH can be of hypothalamic or pituitary origin. Cases were arbitrarily assigned to the pituitary category for simplicity.