Diagnosis
Diagnosis of Gorlin syndrome is vital
In the past it was common for families to remain undiagnosed for several generations despite having been seen by doctors from a variety of disciplines.
Diagnosis in a child at 50% risk of having inherited the condition may not be easy because of the extreme variation in expression, both within and between families. Some children may have no rib anomalies whilst others have the ‘typical face’ without other signs.
For apparently isolated cased, detailed examination and x-ray investigation of the parents should be undertaken before concluding that a child’s condition is the result of a new mutation. If an adult has no physical signs, no pertinent history and normal radiology, it is unlikely that he or she has Gorlin syndrome.
Confident diagnosis is vital for subsequent surveillance for complications such as BCCs and jaw cysts, and for giving genetic information. Clinically it relies on a detailed family history, and physical and x-ray examinations.
Verifiying a diagnosis with X-rays
To verify a clinical diagnosis of Gorlin syndrome, AP and lateral X-rays of the skull, an orthopantogram (OPG), chest X-rays, and spinal X-ray are usually required.
- X-rays should be avoided in childhood if the diagnosis is obvious without them or if a known mutation exists in the family.
- If X-rays have previously been taken (i.e., before the diagnosis of Gorlin syndrome is being considered) it is preferable to obtain and review the originals, rather than repeat them because individuals with the condition are susceptible to x-radiation.
- Even when present, bifid ribs, bifid vertebrae, and falx calcification are often not mentioned in formal reports of radiographic findings as these can also be normal variations in the general population.
- X-ray findings may be helpful in suggesting or confirming the diagnosis in young children with cardiac fibromas, cleft lip/palate, polydactyly, or macrocephaly.
Pre-symptomatic and pre-natal diagnosis is possible by gene tracking using DNA markers from 9q22.3-q31. For an individual family this will depend upon the availability of DNA samples from appropriate family members. There are several highly informative DNA markers within and flanking the gene, resulting in a high accuracy of prediction.
Reviewed and verified by Medical Advisers in conjunction with the Gorlin Syndrome Group, October 2022.
Diagnosis Criterion
Gorlin Syndrome is diagnosed in individuals with two major diagnostic criteria and one minor diagnostic criterion or one major and three minor diagnostic criteria.
These criteria are based on examination of family cases in England, a land not noted for excessive sunlight. The numbers of BCCs acceptable as a major criterion will vary according to the climate and will need adaptation for countries such as Australia.
Major Criteria
- Lamellar (sheet like) calcification of the falx (fold in membrane of the brain descending vertically between the two halves of the brain) or clear evidence of calcification in an individual younger than age 20 years. Falx calcification is nearly always present and is visible on anteroposterior (AP) X-rays of the skull after 20 years.
- Odontogenic keratocystsadd an explanation here (jaw cysts) histologically seen on orthopantogram as an area of translucency.
- Palmar or planta pits (small blemishes on palms of hands and soles of feet) – two or more; particularly useful in diagnosis and more pronounced when the hands and feet are soaked in warm water for up to ten minutes. Pits may appear as white ‘punched out’ or pink ‘pin prick’ lesions.
- Multiple BCCs (>5 in a lifetime) or a BCC before age 30 years. Provision needs to be made for decreased risk of BCC in dark skinned races and increased risk in whites living in hot sunny climates.
- First degree relatives with Gorlin syndrome.
Minor criteria
- Childhood medulloblastoma (also called primitive neuroectodermal tumour).
- Lympho-mesenteric and pleural cysts.
- Cleft lip/palate.
- Vertebral/rib anomalies observed on chest X-ray: bifid/splayed/extra ribs, bifid vertebrae.
- Preaxial or postaxial polydactyly.
- Ovarian/cardiac fibromas.
- Ocular anomalies (cataract, development defects, and pigmentary changes of the retinal epithelium).
It is worth noting that some of the symptoms listed under minor criteria are rare. Speak to your doctor if you have worries or concerns about any aspect of the condition.
Reviewed and verified by Medical Advisers in conjunction with the Gorlin Syndrome Group 20/10/2022
Prognosis
Because of the variability, presumably due to the other genes in a dosage sensitive pathway, members of a family may be affected to different degrees.
There is no evidence in the British studies that children are more severely affected than their parents, although jaw cysts and basal cell carcinomas may be detected earlier through surveillance and may give the impression that these features have occurred at an earlier age.
The skeletal signs are non-progressive and are not consistent between family members.
10% of adults with the syndrome develop neither jaw cysts nor basal cell carcinomas. It is unusual for new jaw cysts to appear from about the mid-thirties. A child where the diagnosis is made on histological examination of an isolated lesion will not necessarily develop a large number of basal cell carcinoma later.
The British studies gave a clinical impression that some families seem especially prone to develop BCCs – occurring at a younger age and in greater numbers – than other families, in which members develop relatively few BCCs, and perhaps much later in life.
The congenital malformations, however, generally do not follow a family-specific pattern: it’s unusual for several family members to be severely affected.
Information provided by Prof Peter A Farndon, MD FRCP
Reviewed and verified by Medical Advisers in conjunction with the Gorlin Syndrome Group, October 2022
Guidance
Of concern to many individuals with Gorlin Syndrome is the risk from medical diagnostic procedures.
The table in the following link gives effective dose and equivalent periods of natural background radiation from diagnostic medical exposures. Visit GOV.UK for information.
If you have concerns about any aspect of the diagnostic procedures being offered to you then it is important that you speak to your doctor.
Reviewed and verified by Medical Advisers in conjunction with the Gorlin Syndrome Group, October 2022