Pallister Hall Syndrome

Classification according to ICD-10
D33.0	Benign neoplasm of the brain, supratentorial
ICD-10 online (WHO version 2019)

The Pallister-Hall syndrome (PHS) is a very rare congenital malformation syndrome with the main features hamartoma in the hypothalamus , hypopituitarism , anal atresia , postaxial polydactyly .

Synonyms are: Hall-Pallister syndrome; Ralpha-Sydrom, anagram for R enal A Nal L un- P olydaktylie- H amartoblastom syndrome; 4H syndrome (Hypothalamic-Hamartoblastoma-Hyperphalangeal-Hypoendocrine-Hypoplastic anus Syndrome); Hamartopolydactyly; Mishap, anagram for M icrocephalus- I mperforate anus S yndaktylie- H amartoblastoma- A BNORMAL lung lobulation- P olydaktyl syndromes; Hamartoma in the hypothalamus area - polydactyly

The name refers to the first authors of the first description from 1980 by the Canadian pediatrician and human geneticist Judith Goslin Hall (* 1939) and the American pediatrician and human geneticist Philip D. Pallister (* 1920).

distribution

The frequency is given as less than 1 in 1,000,000, inheritance is autosomal dominant . About 100 patients have been described to date.

root cause

The disease are mutations in GLI3 - gene on locus 7p14.1 based on which a transcription factor by the coded Hedgehog signaling pathway is activated.

Clinical manifestations

Clinical criteria are:

Intrauterine growth retardation
Pituitary dysfunction (hypopituitarism), hypothalamic hamartoma
Facial dysmorphism flat midface, wide fontanelle , long philtrum , upward nostrils frenulum , dysplastic ears, Microtia , microphthalmia , coloboma , cleft lip and palate , neonatal teeth, epiglottis column, also Larynxatresie
Postaxial polydactyly, usually on the 3rd or 4th finger, syndactyly , hyperextensible hip and knee joints
Nail hypoplasia , short extremities
Genital malformations with micropenis , cryptorchidism , hypospadias , less often renal agenesis , hydrometrocolpos
Anal atresia , Hirschsprung's disease

diagnosis

In patients with a familial history of PHS, two criteria must be present for clinical diagnosis:

(1) Hypothalamic hamartoma
(2) polydactyly

The X-ray images typically include:

flat sella turcica , cranial bone, prominent occiput
small thorax with thin ribs , sometimes abnormal lung lobes , multiple ossification centers in the sternum
Scoliosis , flattened cervical vertebrae
short and wide radius

In the MRI a mass hypothalamic isointense with gray matter in the midline.

The diagnosis can be confirmed by molecular genetics .

A hypothalamic hamartoma can already be detected intrauterine by fine ultrasound or MRI.

Differential diagnosis

The following are to be distinguished:

literature

JG Hall: The early history of Pallister-Hall syndrome-Buried treasure of a sort. In: Genes. 589 (2), Sep 10, 2016, pp. 100-103. doi: 10.1016 / j.gene.2016.01.003 . PMID 26768579 .

Individual evidence

↑ ^a ^b ^c ^d 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 .
↑ ^a ^b ^c ^d ^e Pallister Hall Syndrome. In: Orphanet (Rare Disease Database).
↑ JG Hall, PD Pallister, SK Clarren, JB Beckwith, FW Wiglesworth, FC Fraser, S. Cho, PJ Benke, SD Reed: Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly – a new syndrome? Part I: clinical, causal, and pathogenetic considerations. In: American journal of medical genetics. Volume 7, No. 1, 1980, pp. 47-74, doi: 10.1002 / ajmg.1320070110 . PMID 7211952 .
↑ Pallister-Hall syndrome. In: Online Mendelian Inheritance in Man . (English)
Jump up ↑ S. Jaiman, H. Nalluri, N. Aziz, G. Kolar: Pallister-Hall syndrome presenting as an intrauterine fetal demise at 39 weeks' gestation. In: Indian journal of pathology & microbiology. Volume 55, No. 1, 2012 Jan-Mar, pp. 100-103, doi: 10.4103 / 0377-4929.94873 . PMID 22499313 .

Web links

LG Biesecker: Pallister-Hall syndrome. PMID 20301638
Genetics Home Reference
Rare Diseases

[Leiber-1] 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 .

[Orpha-2] Pallister Hall Syndrome. In: Orphanet (Rare Disease Database).

[3] JG Hall, PD Pallister, SK Clarren, JB Beckwith, FW Wiglesworth, FC Fraser, S. Cho, PJ Benke, SD Reed: Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly – a new syndrome? Part I: clinical, causal, and pathogenetic considerations. In: American journal of medical genetics. Volume 7, No. 1, 1980, pp. 47-74, doi: 10.1002 / ajmg.1320070110 . PMID 7211952 .

[4] Pallister-Hall syndrome. In: Online Mendelian Inheritance in Man . (English)

[5] Jump up ↑ S. Jaiman, H. Nalluri, N. Aziz, G. Kolar: Pallister-Hall syndrome presenting as an intrauterine fetal demise at 39 weeks' gestation. In: Indian journal of pathology & microbiology. Volume 55, No. 1, 2012 Jan-Mar, pp. 100-103, doi: 10.4103 / 0377-4929.94873 . PMID 22499313 .