Wolf-Hirschhorn syndrome / deletion 4p & 4p- syndrome
Syndrome Synonyms
- WHS
- Wolf Syndrome
- Wolf-Hirschhorn Chromosome Region (WHCR)
- WHCR
- Chromosome 4, Partial Deletion 4p
- Partial Deletion of the Short Arm of Chromosome 4
- Chromosome 4, Partial Monosomy 4p
- 4p- Syndrome, Partial
Signs and symptoms
The most common abnormalties seen include severe to profound mental retardation, microcephaly, seizures, hypotonia, and cleft lip and/or palate. Characteristic facial features, include strabismus, hypertelorism, down-turned "fishlike" mouth, short upper lip and philtrum, small chin, ear tags or pits, and cranial asymmetry. Occasional abnormalities include heart defects, hypospadias, scoliosis, ptosis, fused teeth, hearing loss, delayed bone age, low hairline with webbed neck, and renal anomalies.
Genetics
Wolf-Hirshhorn syndrome is caused by a partial deletion of the short arm of chromosome 4, particularly in the region of WHSC1 and WHSC2. About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation. In the cases of familial translocation, there is a 2 to 1 excess of maternal transmission. Of the de novo cases, 80% are paternally derived. The symptoms and phenotype do not differ based on the size of the deletion. The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescent in situ hybridization (FISH). Genetic testing and genetic counseling is offered to affected families.
Clinical age description
During the first year of life Patients are usually small for gestational age with an average birth weight of 2000 g at term. Muscular hypotonia is remarkable. The characteristic craniofacial phenotype consisting of microcephaly, craniofacial asymmetry, high forehead, broad nasal bridge with prominent glabella, hypertelorism, deep-set and dysmorphic ears, preauricular tags, short philtrum, and downturned corners of the mouth, is present at birth and usually gives a clue to the correct diagnosis (Battaglia et al., 1999; Wieczorek et al., 2000). Nearly 35% of patients die during the first year of life, due to congenital heart defects (Shannon et al,. 2001).
During toddler's age The usually severe psychomotor retardation becomes obvious. Patients have a short stature and hypodontia. The fingers are tapering and sometimes ulnar deviated. The feet are characterized by camptodactyly and under- and overriding toes. This period of life is often complicated by respiratory tract infections. Seizures often occur in this period of life, medical treatment is often difficult. Only a very few patients with WHS learn to walk without support during this time. Those, who are able to walk, learn it between the age of 3 and 5 years. Active speech is also uncommon in patients with WHS, only a few patients are able to speak some words. The first two years of life mortality rate is 21% (Battaglia et al., 1999;
Later childhood and adolescence The facial phenotype is less characteristic in later life. Differentiation from other chromosomal aberrations is much more difficult (Ogle et al., 1996; Wheeler et al.,1995; Rauch et al., 2001) described a patient with a small interstitial deletion restricted to the WHSCR who presented only with a partial WHS phenotype consisting of low body weight for height, speech delay, and minor facial anomalies. Short stature, microcephaly,
Management including treatment
There is no specific treatment. Physiotherapy and occupational therapy are recommended. Some patients require physical aids, e.g. wheel chair, splints, hearing aids etc. Patients with congenital heart defects, clubfeet, and cryptorchidism have to be surgically treated. Those with seizures need recurrent EEGs and antiepileptic drugs (Zankl et al., 2001).
Resource Information
- Chromosome Deletion Outreach, Inc.
P.O. Box 724
Boca Raton, FL 33429-0724 USA
Tel: 561.395.4252
Fax: 561.395.4252
Email: info@chromodisorder.org
Internet: chromodisorder.org
- 4p- Support Group
c/o Amanda Lortz, President
131 Green Cook Road
Sunbury, Ohio 43074
president@4p-supportgroup.org
- Wolf-Hirschhorn Syndrome Support Group
1 Hawthorne Villas
Holmes Chapel
Crewe, CW4 7AR United Kingdom
Tel: 01477 549465
Email: whs@webk.co.uk
Internet: whs.webk.co.uk/
- World Health Organization (WHO) Regional Office for the Americas (AMRO)
Pan American Health Organization (PAHO)
525 23rd Street NW Washington, DC 20037
Tel: 202.974.3000
Fax: 202.974.3663
Email: postmaster@paho.org
Internet: http://www.who.ch/
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