Genital abnormalities in Pallister-Hall syndrome: Report of two patients and review of the literature.
We describe two patients with Pallister-Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ynarumi@shinshu-u.ac.jp
Yoko
Y
Narumi
Tomoki
T
Kosho
Goro
G
Tsuruta
Masaaki
M
Shiohara
Ei
E
Shimazaki
Tetsuo
T
Mori
Ayako
A
Shimizu
Yasuhiko
Y
Igawa
Shuji
S
Nishizawa
Kimiyo
K
Takagi
Rie
R
Kawamura
Keiko
K
Wakui
Yoshimitsu
Y
Fukushima
D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D054975:Pallister-Hall Syndrome / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D014564:Urogenital Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3
D018389:Codon, Nonsense; C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3; D004247:DNA