Holoprosencephaly

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Classification according to ICD-10
Q04.2 Holoprosencephaly Syndrome
ICD-10 online (WHO version 2019)

The holoprosencephaly ( HPE ) is a prenatally (vorgeburtlich) resulting malformation in the region of the forebrain and the face .

frequency

Holoprosencephaly occurs in about one to four out of 1,000 pregnancies in children, making it the most common congenital brain malformation. However, since most babies are not viable, only one in 2,500 to 16,000 children with holoprosencephaly is born alive due to the high intrauterine mortality . Girls are more often affected than boys ( gynecotropia ) and the malformation is more often found in children of very young mothers.

Emergence

The malformation occurs around the third to sixth week of the embryo due to incomplete division of the forebrain as a result of a disruption in the midline developmental field of the head: the prosencephalon ( forebrain ), which is made up of the telencephalon ( endbrain ), does not completely divide or differentiate ) and the diencephalon ( interbrain ).

causes

Not much is known about the exact causes ( etiology ) of holoprosencephaly. In most cases the occurrence is random (sporadic), but apparently a genetic deficiency in cholesterol can (partly) cause the developmental disorder. As risk factors are also considered diabetes mellitus of the pregnant woman, viral disease of the fetus, toxoplasmosis , various teratogens such and environmental factors. B. hyperglycemia , hypocholesterolemia , retinoic acid and ethanol , which can have an influence.

Statistically, around 50 out of 100 children show clear deviations on the chromosomal level (e.g. trisomies) and in another 20 changes can be detected using special molecular genetic techniques. The cause of holoprosencephaly in the remaining 30% of children cannot currently be linked to genetic reasons.

More than 25 diseases with a genetic background are associated with an increased likelihood of holoprosencephaly. These also include chromosome peculiarities such as triploidy , trisomy 13 (Pätau syndrome), trisomy 18 (Edwards syndrome), 18p syndrome , pseudotrisomy 13 syndrome , chromosome 7q syndrome , De Grouchy syndrome , short rib polydactyly syndrome and Joubert syndrome .

Various holoprosencephaly loci (HPE) have so far been found in studies of genetic factors :

  • 4 frequent SHH on 7q36, ZIC2 on 13q32, SIX3 on 2p21, TGIF on 18p11
  • 10 rare PTCH1 on 9q22, GLI2 on 2q14, FOXH1 on 8q24, TDGF1 on 3p21, DISP1 on 1q42, NODAL on 10q22, FGF8 on 10q24, GAS1 on 9q21, DLL1 on 6q27 and CDON on 11q23-q24

The inheritance appears to be autosomal dominant or autosomal recessive.

In the context of syndromes

  • Agnathia - holoprosencephaly - situs inversus
  • Hartsfield syndrome , synonym: holoprosencephaly-ectrodactyly-cleft lip and palate syndrome
  • Genoa syndrome , synonyms: Camera-Lituania-Cohen syndrome; Holoprosencephaly - Craniosynostosis
  • Pseudotrisomy 13 syndrome , synonym: holoprosencephaly - postaxial polydactyly
  • Morse-Rawnsley-Sargent Syndrome , synonyms: holoprosencephaly-fetal akinesia / hypokinesia sequence syndrome; Holoprosencephaly-hypokinesia-congenital contractures syndrome
  • Steinfeld syndrome , synonym: holoprosencephaly - radius, heart and kidney malformations
  • Stenosis of the piriform aperture, congenital, with holoprosencephaly

Clinical features

Prenatal ultrasound image of alobar holoprosencephaly at the level of the choroid plexus
Prenatal ultrasound image of alobar holoprosencephaly at the midbrain level
Ultrasound image at 8 months of age, only narrow ventricular system
Lobar form, sonogram at 4 months of age

The manifestation shows a broad spectrum: clinically inconspicuous mutation carriers, cleft lip and palate (also median pseudo -clefts ), microglossia , slight forms (e.g. with only one central incisor , hypotelorism / eyes close together) also occur such as arrhinencephaly , corpus callosum agenesis , agenesis of the pituitary gland, and disorders with cyclopia . Around nine out of ten children have other malformations.

Classification

The classic classification according to increasing severity and anatomical changes according to DeMyer differentiates:

  • lobar holoprosencephaly (separation has largely occurred , complete interhemispheric gap, two lateral ventricles with rudimentary connection)
  • semilobar holoprosencephaly (partial separation, posterior interhemispheric gap with rudimentary hemispheres , a cerebral ventricle)
  • alobar holoprosencephaly (no separation, no interhemispheric gap , one cerebral ventricle )

There are also microforms

and special forms

  • Medium interhemispheric fusion variant
  • septopraoptic holoprosencephaly

diagnosis

The diagnosis can be made prenatally within the framework of prenatal diagnostics , in particular through fine ultrasound examinations in the second trimester , but sometimes even earlier. While the determination of the alobar and semilobar forms is often fairly straightforward, that of lobar holoprosencephaly is more complicated.

After the prenatal diagnosis has been confirmed, the parents-to-be can decide to terminate the pregnancy for medical reasons or, based on their knowledge, prepare for the birth of the child and make appropriate preparations (choice of clinic, etc.).

After birth, the cross-sectional imaging methods sonography and magnetic resonance tomography are the methods of choice.

Differential diagnosis

The following are to be distinguished:

Therapy and consequences

No therapy is currently known, only the symptoms can be treated if necessary ( symptomatic therapy ). The death rate in affected children is very high during pregnancy. The prognosis for life expectancy and development of newborn children with holoprosencephaly is usually unfavorable: Children with a severe form of the malformation usually die within the first few months after birth.

The prognosis is worse with the alobar form than with the semilobar or lobar form. Experience has shown that around 9 out of 10 children with the alobaric form die within the first year of life. Children who survive the first year may well reach adulthood. Depending on the severity, cognitive and physical impairments are to be expected in them, as well as neurological abnormalities (e.g. epilepsy ), lack of or limited development of spoken language, difficulty sleeping and the like. a.

literature

  • C. Dubourg, C. Bendavid, L. Pasquier, C. Henry, S. Odent, V. David: Holoprosencephaly. In: Orphanet J Rare Dis. 2; 2, Feb 2007, p. 8. PMID 17274816 , PMC 1802747 (free full text)
  • P. Reimer, PM Parizel, F.-A. Stichnoth (Editor): Clinical MR Imaging. A practical approach. Springer, 2nd edition 2006, ISBN 3-540-31530-6

Individual evidence

  1. ↑ a b c d Holoprosencephaly. In: Orphanet (Rare Disease Database).
  2. ↑ W. Schuster, D. Färber (editor): Children's radiology. Imaging diagnostics. Springer 1996, ISBN 3-540-60224-0 . Vol. 1, p. 482ff
  3. ↑ a b GeneReviews
  4. ↑ Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  5. ↑ Emedicine
  6. ↑ Agnathia - holoprosencephaly - situs inversus. In: Orphanet (Rare Disease Database).
  7. ^ Hartsfield syndrome. In: Orphanet (Rare Disease Database).
  8. ↑ Holoprosencephaly - Craniosynostosis. In: Orphanet (Rare Disease Database).
  9. ↑ Holoprosencephaly-hypokinesia-congenital contracture syndrome. In: Orphanet (Rare Disease Database).
  10. ^ Steinfeld syndrome. In: Orphanet (Rare Disease Database).
  11. ↑ Stenosis of the piriform aperture, congenital, with holoprosencephaly. In: Orphanet (Rare Disease Database).
  12. ↑ W. DeMyer, W. Zeman, CG Palmer: The Face Predicts The Brain: Diagnostic Significance Of Median Facial Anomalies For holoprosencephaly (Arhinencephaly). In: Pediatrics. Volume 34, August 1964, pp. 256-263, PMID 14211086 .
  13. ↑ Holoprosencephaly, lobar. In: Orphanet (Rare Disease Database).
  14. ↑ Holoprosencephaly, semilobar. In: Orphanet (Rare Disease Database).
  15. ↑ Holoprosencephaly, alobar. In: Orphanet (Rare Disease Database).
  16. ↑ Holoprosencephaly, microform. In: Orphanet (Rare Disease Database).
  17. ↑ Mean interhemispheric fusion variant of holoprosencephaly. In: Orphanet (Rare Disease Database).
  18. ↑ Holoprosencephaly, septopraoptic. In: Orphanet (Rare Disease Database).
  19. ^ V. Hofmann, KH Deeg, PF Hoyer: Ultrasound diagnostics in paediatrics and pediatric surgery. Textbook and atlas. Thieme 2005, ISBN 3-13-100953-5

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