Cutis verticis gyrata and chromosomal fragile sites

American Journal of Medical Genetics 38:249-250 (1991)

Letter to the Editor Cutis Verticis Gyrata and Chromosomal Fragile Sites To the Editor: Cutis verticis gyrata (CVG) is a rare condition that has been described as secondary to different pathological situations or as primary; a few apparently normal patients with CVG have been reported [Akesson, 19641. Some classifications have already been proposed, and familial and nonfamilial cases with chromosomal abnormalities have been described [Marini et al., 19891. The prevalence in the general population has been estimated as 1/100,000for males and 2.6/10,000,000for females [Akesson, 19641, whereas the prevalence in institutionalized mentally retarded males seems to be higher, from 0.21% to 1%[MacGillivray, 19671. It has been suggested that the higher prevalence in males could be due to hormonal factors or, more simply, to an easier detection of the abnormality because of shorter hair [Polan and Butterworth, 19531. We have recently observed 3 mentally retarded individuals with CVG (Fig.l),2males and 1female. Clinical manifestations and karyotypes of these subjects are shown in Table I. In all subjects, the CVG was first observed after puberty. It was not associated with microcephaly, but other minor anomalies were present. We believe that these observations could support the hypothesis that CVG, at least in part, is not a homogeneous disorder but can be due to different etiological factors, with a common pathogenetic mechanism represented by neonatal lymphoedema, which could be partially reabsorbed in postnatal life, causing its onset [Marini et al., 19891. Our patients did not show microcephaly, so we can exclude the discrepancy between skull and scalp growth as an etiological factor; the fragile X male showed, besides CVG, large and lop ears, macroorchidism, high arched palate, and venous varices, most likely depending on a connective tissue disorder, as has been described for fragile X patients [Hagerman et al., 19843.On the other

Fig. 1. CVG with longitudinal creases in the patient with fra 10q25.

hand, fra 10q25 is now considered to be a normal variant, but our observation, if further confirmed, could indicate the existence of an association not yet described in the literature. At present, it is probably safer to consider this as simply coincidental. We suggest that the possible presence of chromosomal fragile sites must be considered in cases of CVG and that the higher frequency of CVG in males after puberty could also be supported by the association with the fragile X chromosome, and it could be an additional clinical finding for the diagnosis of aged fragile X patients.

REFERENCES Akesson HO (1964): Cutis verticis gyrata and mental deficiency in Sweden: I) Epidemiologic and clinical aspects. Acta Med Scand 175:115-127. Hagerman RJ, Van Housen K, Smith ACM, McGavran L (1984):Consideration of connective tissue dysfunction in the fragile X syndrome. Am J Med Genet 17:lll-121. MacGillivray RC (1967):Cutis verticis gyrata and mental retardation. Scot Med J 12:450-454.

TABLE I. Clinical Manifestations and Karyotype of the Three Subjects Subject

B.P. J.L. N.M.

Age (years)

56 44 14

Sex M M F

Height

TV

HC

(crn)

(cc)

(crn)

CVG

Karyotype

181 178 150

35 50

56.8 57 50

Present Present Present

3% fra Xq27-28 12%fra 10q25 6% fra Xq27-28

* TV, testicular volume; HC, head circumference. Received for publication August 7, 1989; revision received May 29, 1990. Address reprint requests to S.A. Musumeci, MD, Dept. Neurology, OASI Institute, 94018 'Ikoina (EN), Italy.

0 1991 Wiley-Liss, Inc.

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Musumeci et al.

Marini R, Cappa M, Neri G (1989): Cutis verticis gyrata and chromosomal abnormalities. Am J Dis Child 143969-270. Polan S, Butterworth T (1953): Cutis verticis gyrata: Review with report of seven new cases. Am J Ment Defic 57:613-631.

S.A. Musumeci R. Ferri M. Viglianesi M. Elia R.M. Ragusa P. Bergonzi 0-1 Institute for Research on Mental Retardation and Brain Aging Troina, Italy