HOLOPROSENCEPHALY

Holoprosencephaly are complex developmental abnormalities of the forebrain that are thought to be due to a failure of normal diverticulation of the embryonic prosencephalon. They are characterized by abnormal midline separation of the cerebral hemispheres and diencephalic structures. There is a wide spectrum of severity (1-8). Diagnosis of holoprosencephaly has been reported as early as 10.5 weeks of gestation (5). Three types are recognized depending on the degree of forebrain cleavage (DeMeyer Classification) (9).

Etiology And Pathogenesis

Table Comparing the Three Types of Holoprosencephaly

Differential Diagnosis

CLASSIFICATION

1. Alobar Holoprosencephaly
2. Semilobar Holoprosencephaly
3. Lobar Holoprosencephaly

ASSOCIATIONS

1. Chromosomal aberrations (20-67%):
• Trisomy 13 (1)
• Triploidy (2)
• Trisomy 18 (3,4), mosaic 18p deletion (5).
• Others include del(13q), del(18p), dup(3p), del(7)(q36), del(21)(q22.3), -14,+t(13;14) (6-8).
• Multiple chromosomal defects in 39% (1).
2. Dandy Walker Malformation
3. Astomia-Agnathia-Holoprosencephaly association

SYNDROMES THAT HAVE HOLOPROSENCEHALY

AS A MANIFESTATION

• Agnathia-holoprosencephaly-situs inversus triad.
• Anosmia-radiohumeral synostosis syndrome.
• Aprosencephaly syndrome (aprosencephaly; radial aplasia;genital anomalies).
• Campomelic dysplasia.
• COH syndrome (Childrens Orthopedic Hospital) – cloverleaf skull; proptosis; low nasal bridge; short upturned nose; downturned mouth; narrow palate; duplication of the thumb; small fifth fingers.
• DiGeorge syndrome.
• Fitch syndrome (arrhinencephaly; callosal agenesis; hydrocephalus; absent left leaf of diaphragm; VSD; absent fifth fingernails).
• Genoa syndrome (holoprosencephaly; carniosynostosis).
• Goldenhar spectrum – arrhinencephaly.
• Kallmans syndrome.
• Meckel syndrome.
• Pallister-Hall syndrome.
• Perrin syndrome (anosmia; mental deficiency; hypogonadism; congenital ichthyosis).
• Pseudotrisomy 13.
• Steinfeld syndrome (holoprosencephaly; bilateral hypoplasia of radius and ulna; absent thumbs; midline cleft lip and palate; absent philtrum; congenital heart defect; renal dysplasia; absent gallbladder).
• Vasadi syndrome (10) (cleft lip/palate; growth restriction; mental retardation; supernumerary finger; duplicated halluces; lingual nodule).
• Holoprosencephaly-hypokinesia syndrome (Morse syndrome).

REFERENCES

1. Snijders RJM, Farrias M, von Kaisenberg C et.al. Fetal abnormalities. In: Snijders RJ, Nicolaides KH (eds) Ultrasound markers for fetal chromosomal defects. Parthenon Publishers, Carnforth, UK 1996:1-62.
2. Greene MF, Benacerraf BR, Frigoletto FD Jr. Reliable criteria for the prenatal sonographic diagnosis of alobar holoprosencephaly. Am J Obstet Gynecol 1987;156:687-689.
3. Berry SM, Gosden C, Snijders RJ et.al. Fetal holoprosencephaly: associated malformations and chromosomal defects. Fetal Diagn Ther 1990;5:92-99.
4. Nicolaides KH, Snijders RJM, Godsen CM et.al. Ultrasonographically detectable markers of fetal chromosomal abnormalities. Lancet 1992;340:704-707.
5. Wong HS, Lam YH, Tang MHY. First-trimester ultrasound diagnosis of holoprosencephaly: three case reports. Ultrasound Obstet Gynecol 1999;13:356-359.2
6. Peebles DM. Holoprosencephaly. Prenat Diagn 1998;18:477-480.
7. Eastbrook LL, Rao RW, Donahue RP et.al. Holoprosencephaly in an infant with a minute deletion of chromosome 21 (q22.3). Am J Med Genet 1990;36:306-309.
8. Chervenak FA, Isaacson G, Hobbins JC et.al. Diagnosis and management of fetal holoprosencephaly. Obstet Gynecol 1985;66:322-326.
9. DeMeyer W. Holoprosencephaly. In: Vinken PJ, Bruyn GW (eds). Handbook of clinical neurology. Elsevier, Amsterdam 1977;30:431-478.
10. Achiron R, Achiron A, Lipitz S et.al. Holoprosencephaly: alobar. Fetus 1994;7422:9-12.