- Wolf-Hirschhorn Syndrome.

Wolf-Hirschhorn Syndrome

*Pathophysiology:-
results from deletion of the distal short arm of chromosome no 4 (1).

* Clinically, the minimal diagnostic criteria for Wolf-Hirschhorn syndrome (ie, ‘‘core’’ phenotype) consists of typical facial appearance , mental retardation, growth delay, hypotonia and seizures (or EEG anomalies)(2).

* Different categories of the Wolf-Hirschhorn syndrome phenotype are defined according to the extent of the chromosome.4 deletion(2):-

• 1st category :- caused by small deletion that is usually associated with a mild phenotype, lacking major malformations. This category is likely under-diagnosed.
• 2nd category :- caused by large deletions that cause the widely recognizable Wolf-Hirschhorn syndrome phenotype.
• 3rd category :- caused by very large deletions that cause a severe phenotype that can hardly be defined as typical Wolf-Hirschhorn syndrome.

* Factors affecting prognosis include (2):-

• extent of the deletion.
• occurrence of complex chromosome anomalies.
• severity of seizures.

*Karyotype (1):-
46,xx,4p-(female).
46,xy,4p-(male).
(4p- means that the short arm of chromosome 4 is shorter than normal).

* Clinical picture(3),(4):-

• Growth retardation.
• CNS:- Developmental delay and mental retardation of varying degree,microcephaly, seizures, congenital hypotonia with muscle hypotrophy particularly of the lower limbs.
• Skull:- Frontal bossing, high frontal hairline, hemangioma over forehead or glabella, scalp defect with or without underlying bony defect.
• Face:- Characteristic features including prominent glabella, hypertelorism, broad beaked nose, and frontal bossing, collectively described as "Greek warrior helmet" facies.
• Eyes:- Hypertelorism, down-slanting palpebral fissures, epicanthal folds, strabismus, coloboma, proptosis.
• Nose :- Broad or beaked nose, nasolacrimal duct stenosis or atresia
• Mouth:- Short upper lip, short philtrum, cleft lip or palate, bifid uvula, carplike mouth, micrognathia, retrognathia
• Teeth:- Hypodontia
• Ears:- Low-set ears; large, floppy, or misshapen ears; microtia; preauricular dimples; chronic otitis media with effusion; sensorineural hearing loss.
• Cardiovascular:- Atrial septal defect, ventricular septal defect.
• Pulmonary:- lung hypoplasia secondary to diaphragmatic hernia.
• GIT:- Diastasis recti, umbilical or inguinal hernias, accessory spleens, absent gallbladder, diaphragmatic hernia, intestinal malrotation.
• Genitourinary:- Hypoplastic kidneys, cystic dysplastic kidneys, unilateral renal agenesis, hydronephrosis, exstrophy of bladder, hypoplastic external genitalia.
• Skeletal:- Long slender fingers with additional flexion creases, long narrow chest, hypoplastic widely spaced nipples, hypoplasia or duplication of thumbs and great toes, hypoplasia of pubic bones.

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*References:-
(1) Principles of histology vol1,staff members ,faculty of medicine,mansoura university,ch3,p.g74.
(2) Zollino M, Murdolo M, Marangi G, et al. On the nosology and pathogenesis of
Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients
and literature review. Am J Med Genet C Semin Med Genet. Nov 15 2008;148C(4):257-69. [Medline].
(3)Battaglia A, Carey JC, Wright TJ. Wolf-Hirschhorn (4p-) syndrome. Adv Pediatr. 2001;48:75-113. [Medline].
(4)South ST, Whitby H, Battaglia A, Carey JC, Brothman AR. Comprehensive analysis of Wolf-Hirschhorn syndrome using array CGH indicates a high prevalence of translocations. Eur J Hum Genet. Jan 2008;16(1):45-52. [Medline]. [Full Text].