Cytogenetics: a new tool for early diagnosis and prognosis of tuberous sclerosis?

Sir,

Chromosomes are rod-shaped structures with two chromatids held together at centromere. In acrocentric subtype of chromosomes i.e. chromosome nos. 13, 14, 15, 21, 22, centromere lies near one end.[12] Sticky substance formed during meiosis keeps tips of short arms closer and grouping of chromosomes occurs.[3] It is known as acrocentric association (A.A.).[2] Previously acrocentric association has been detected in Down's syndrome, Turner's syndrome, Klinefelter's syndrome and in recurrent aborters.[4] In fact, the authors have noticed significant A.A. in a 10- year-old girl with Monilethrix. A.A. accounts for elevated incidence of chromosomal rearrangements and consequently can cause chromosomal diseases.[2]

A 33-year-old woman presented to us with multiple erythematous/ hyperpigmented angiofibroma over nasolabial fold, nose, cheeks. In addition, the patient had multiple Shagreen patches over the back [Figure 1]. Nail examination showed periungual fibroma with onycholysis involving many of the toe nails and a few finger nails [Figure 2]. Dental examination showed presence of pitting.

Figure 1

Multiple Shagreen patches in the female patient

Figure 2

Periungual fibroma in the finger nails of the female patient. Toe nails are also involved

A 25-year-old man, sibling of the above patient, presented with similar number of facial lesions (angiofibroma), limited involvement of nails and single Shagreen patch [Figures 3 and 4]. Based on the clinical features, we diagnosed tuberous sclerosis in both patients.

Figure 3

Single Shagreen patch in the male patient

Figure 4

Finger nails are normal in the male patient. Toe nails are involved

Cytogenetic study was done for both the patients, and results showed 60% of A.A. in the first patient; 36%, in the second patient; while A.A. was 27% for the control of the first patient and 18% for the control of the second patient [Figures 5 and 6].

Figure 5

Tetra acrocentric association in the female patient

Figure 6

Di acrocentric association in the male patient

In the present case, high degree of A.A. in patients compared to controls may indicate the diagnostic utility of cytogenetic study in Tuberous Sclerosis; and higher degree of A.A. in the first patient compared to second and more clinical features in the first patient compared to second may indicate utility of cytogenetic study in predicting the extent and severity, when the disease is diagnosed early. Higher degree of acrocentric association in both the patients in comparison to controls may indicate some association between acrocentric association and mutation of TSC1 and TSC2 genes.[5]

Cytogenetic studies have not been extensively applied in genodermatoses. However, the authors feel that detection of Acrocentric Association in genodermatoses like Bloom syndrome, tuberous sclerosis, Monilethrix, may have a predictive value. Hence early detection and counseling both the parents and patients may help them to live and cope with the disease.