Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital anomaly syndrome. The clinical findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD26 Syndromes with limb anomalies as a major feature
H02161 Greig cephalopolysyndactyly syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06501 HH signaling
H02161 Greig cephalopolysyndactyly syndrome
Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG
Title
Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations.
Postaxial polydactyly (PAP) is one of the commonest congenital malformations. Both isolated and syndromic forms of PAP have been reported. PAP is characterized by duplication of the fifth finger/toe on the ulnar/fibular side of hands/feet. A small projection of tissue or scar mark just below the proximal interphalangeal crease can also be the only clinical finding. PAP is clinically classified into type A (PAPA) with fully developed extra digit and type B (PAPB) with incompletely developed digit. PAPA is a genetically heterogeneous disorder and exhibits either autosomal dominant or recessive manner of inheritance. Given that both isolated PAPA1 and PAPB are caused by the mutations in the GLI3 gene, PAPB may be considered as a variant of PAPA1 in genetics.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Structural developmental anomalies primarily affecting one body system
Structural developmental anomalies of the skeleton
LB78 Polydactyly
H01852 Postaxial polydactyly
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06501 HH signaling
H01852 Postaxial polydactyly
Palencia-Campos A, Ullah A, Nevado J, Yildirim R, Unal E, Ciorraga M, Barruz P, Chico L, Piceci-Sparascio F, Guida V, De Luca A, Kayserili H, Ullah I, Burmeister M, Lapunzina P, Ahmad W, Morales AV, Ruiz-Perez VL
Title
GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis-van Creveld syndrome.
Schrauwen I, Giese AP, Aziz A, Lafont DT, Chakchouk I, Santos-Cortez RLP, Lee K, Acharya A, Khan FS, Ullah A, Nickerson DA, Bamshad MJ, Ali G, Riazuddin S, Ansar M, Ahmad W, Ahmed ZM, Leal SM
Title
FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice.
Ullah I, Kakar N, Schrauwen I, Hussain S, Chakchouk I, Liaqat K, Acharya A, Wasif N, Santos-Cortez RLP, Khan S, Aziz A, Lee K, Couthouis J, Horn D, Kragesteen BK, Spielmann M, Thiele H, Nickerson DA, Bamshad MJ, Gitler AD, Ahmad J, Ansar M, Borck G, Ahmad W, Leal SM
Title
Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly.
Polydactyly is the most common hereditary limb anomaly characterized by extra fingers. Preaxial polydactyly (PPD) refers to polydactyly where the additional digit grows toward the first digit of the hand or foot. Mutations in genes including GLI1, GLI3 and SHH/ZRS, involved in Hedgehog pathway, result in PPD.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Structural developmental anomalies primarily affecting one body system
Structural developmental anomalies of the skeleton
LB78 Polydactyly
H02332 Preaxial polydactyly
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06501 HH signaling
H02332 Preaxial polydactyly
Radhakrishna U, Bornholdt D, Scott HS, Patel UC, Rossier C, Engel H, Bottani A, Chandal D, Blouin JL, Solanki JV, Grzeschik KH, Antonarakis SE
Title
The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations.
Pallister-Hall syndrome (PHS) is characterized by polydactyly, hypothalamic hamartoma, and malformations of other parts of the body. Cases with severe malformations are neonatally lethal. PHS is caused by GLI3 mutations.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2F Syndromes with multiple structural anomalies, without predominant body system involvement
H00502 Pallister-Hall syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06501 HH signaling
H00502 Pallister-Hall syndrome
Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG
Title
Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations.
