Wolf-Hirschhorn Syndrome

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Classification according to ICD-10
Q93.3 Deletion of the short arm of chromosome 4 - Wolf-Hirschhorn syndrome
ICD-10 online (WHO version 2019)

The Wolf-Hirschhorn syndrome is a rare congenital genetic disease caused by a so-called structural chromosomal aberration is due to the short arm of chromosome 4th The main symptom is a short stature combined with an extreme delay in mental and physical development and a combination of different malformations. It is named after Ulrich Wolf and Kurt Hirschhorn , who first described the clinical picture independently of one another in 1965.

Synonyms are: Wolf Syndrome; Chromosome 4p syndrome; Deletion 4p, distal; Monosomy 4p, distal; English Chromosome 4p16.3 Deletion Syndrome; Pitt-Rogers-Danks Syndrome; PRDS; Pitt Syndrome; Wittwer Syndrome

distribution

The frequency of Wolf-Hirschhorn syndrome is given in the literature as 1: 50,000 births. Extrapolated to Germany, this would correspond to around 14 newly diagnosed cases every year. In contrast, an American study reports on a total of 120 documented cases in the entire medical literature up to 1998, which can best be explained by the fact that there must be many undetected cases with this disorder. Girls are affected slightly more often than boys.

root cause

The cause is the loss of a small section ( deletion ) at the end of the short arm of chromosome 4 . The deletions described vary in size. The smallest section, the loss of which leads to the typical symptoms, i.e. the so-called critical region, is a region in band 4p16.3 about 165  kilobase-pairs in size. About 85–87% of all deletions arise in the affected individual as new ( de novo ), mostly in the paternal chromosome, so they are not inherited from one of the parents. With de novo deletions, there is no increased risk of repetition for further offspring of the parents. Up to 15% of Wolf-Hirschhorn syndromes are caused by so-called balanced translocations in one parent. The risk of repetition in other children is 50%.

Clinical manifestations

All children have characteristic facial malformations with enlarged eye relief ( hypertelorism ), downward sloping eyelid axes, a wide nose, a shortened philtrum , small jaw ( micrognathia ), downward-pointing corners of the mouth and ear appendages or dimples. Cleft lip or palate are generally described as typical of Wolf-Hirschhorn syndrome, but only occur in larger deletions over 9 Mbp. Typically, children are underweight at birth and their heads are too small. This growth retardation continues after birth; the extent seems to correlate with the extent of the loss of genetic material. Mental development is also delayed in all children. Only about half learn to sit freely and a maximum of one third learn to walk. Only about every fifth child learns to speak at least a few words, with the others being able to communicate in a non-verbal way. About 85% of the affected children develop epilepsy, some of which is difficult to treat, with atypical absences, epileptic spasms, focal clonic seizures, generalized tonic-clonic seizures, myoclonic seizures, side-changing half-sided seizures, tonic seizures, and convulsive and non-convulsive status epileptici. In addition, various organ malformations can occur, which primarily affect the eyes (cleft formation in the iris - coloboma , strabismus), the heart, the kidneys (e.g. renal agenesis ) and the skeletal system in the form of curvature of the spine or clubfeet . Malformations of the genitals ( hypospadias ) have also been described in boys .

Diagnosis

Since it is a terminal deletion on chromosome 4 , this change can be reliably detected with the help of fluorescence in situ hybridization .

therapy

Since Wolf-Hirschhorn syndrome is caused by a chromosome change, there is no cure for it. A variety of symptomatic therapies are used. An energy-rich diet , possibly with the use of feeding tubes ( PEG ), should help to compensate for the underweight. Mental and physical development can be promoted through physiotherapy , occupational therapy and speech therapy . Accompanying malformations may have to be corrected surgically. Epilepsy is treated with medication, preferably with valproic acid , if status epilepticus occurs, also with potassium bromide .

literature

  • U. Wolf, H. Reinwein, R. Porsch, R. Schröter, H. Baitsch: Deficiency on the short arms of a chromosome 4. In: Humangenetik. 1 (5), 1965, pp. 397-413. PMID 5868696
  • K. Hirschhorn, HL Cooper, IL Firschein: Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion. In: Human Genetics. 1 (5), 1965, pp. 479-482. PMID 5895684

Web links

Individual evidence

  1. ↑ a b S. Mercimek-Mahmutoglu, among others: Wolf-Hirschhorn syndrome and early childhood epilepsy. Case report and literature review. In: Monthly Pediatrics. 155, 2006, pp. S68-S72
  2. ^ A. Battaglia et al .: Natural History of Wolf-Hirschhorn Syndrome: Experience With 15 Cases. In: Pediatrics. 103 (4), 1999, pp. 830-836. PMID 10103318
  3. ↑ a b c D. Wieczorek et al .: Effect of the size of the deletion and clinical manifestaion in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion. In: Eur J Hum Genet. 8 (7), 2000, pp. 519-526. PMID 10909852 full text online (English, pdf; 242 kB)
  4. ↑ a b K. Kagitani-Shimono, K. Imai, K. Otani et al: Epilepsy in Wolf-Hirschhorn syndrome (4p-). In: Epilepsia . tape 46 , 2005, pp. 150-155 .