Case Report #1
Joey Jones, a 14-year-old African American child who just seems too tall, is referred to genetic clinic. A physical exam revealed the following parameters and features:
Height = 6 ft, 4 in
Weight = 125 lb
Head circumference = 54 cm
Arm span = 85 in
Upper and lower limbs: Joint laxity and arachnodactyly
Chest: Pectus excavatum
Heart: Soft systolic murmur at the apex
Abdomen: Soft, no hepatosplenomegaly, no masses
An ophthalmologic evaluation showed ectopia lentis and myopia. A cardiologic examination revealed a MVP.
His father was 6 feet, 8 inches tall and died suddenly last year in this 30s. An autopsy showed ruptured aortic aneurysm. A paternal aunt is tall and myopic. Joey’s younger brother is also quite tall for his age.
DIAGNOSIS: The diagnosis for this patient is Marfan Syndrome (MFS).
EVIDENCE FOR SUPPORT: The patient does not have enough features to be diagnosed with Marfan syndrome based on the diagnostic criteria for this condition [The revised Ghent nosology for the Marfan syndrome]. However, the patient fits the diagnostic criteria for Ectopia Lentis Syndrome (ELS). The literature shows that a diagnosis of ELS and the presence of a personal or a family history of aortic aneurysm (which the patient’s father suffered from) is adequate to convert this diagnosis of ELS to Marfan syndrome.
Since the patient has not been clinically diagnosed with MFS, it should be noted that many symptoms of this condition manifest with an increase in age. As the patient is only 14 years old, he/she should be closely monitored to identify any emerging symptoms. Presence of Aortic dissection (an essential criteria for diagnosis of MFS) rarely occurs in childhood.
Further evidence that supports the presence of MFS in this patient are:
2. Ectopia Lentis
3. Excessive linear growth
4. Joint laxity
5. Pectus excavatum
CONFIRMATION OF DIAGNOSIS: The diagnosis of MFS is established based on confirmation of clinical diagnosis. A part of the clinical diagnostic criteria is the presence of a fibrillin-1 (FBN1) mutation. Since we do not have a clinical diagnosis of MFS in our patient it would be beneficial to test for the presence of a mutation in FBN1 gene. The presence of an FBN1 mutation that is associated with cardiovascular disease will confirm the diagnosis of this condition in the patient.
The tests available for this condition are:
1. FBN1 mutation scanning/ Sequence analysis – this test detects sequence variants and has a mutation detection frequency of 70 – 93%.
2. Complementary DNA sequence analysis – This test detects sequence variants and has a mutation detection frequency of 70 – 93%.
3. Deletion/duplication analysis – This test detects exonic and whole gene deletions. The mutation detection frequency for this test is unknown.
The preferred method of testing for this condition is Sequence analysis of FBN1.
Some laboratories that offer this testing are:
1. Mayo Clinic: This laboratory offers FBN1 full...