Fukuyama type congenital progressive muscular dystrophy

(Acta Paediatr Jpn 1991; 33: 261

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269)

Fukuyama Type Congenital Progressive Muscular Dystrophy Makiko Osawa M.D., Yumi Arai, M.D., Harumi Ikenaka, M.D., Hiroko Murasugi, M.D., Nobuko Sugahara, M.D., Sawako Sumida, M.D., Noriko Okada, M.D., Keiko Shishikura, M.D., Haruko Suzuki, M.D., Yoshito Hirayama, M.D., Kyoko Hirasawa, M.D., Yukio Fukuyarna, M.D., Atsuko Tsutsumi, M.D.", Keiko Ito, M.D." and Yukio Uchida, M.D." Department of Pediatrics, *Department of Ophthalmology, Tokyo Women's Medical College, Tokyo Clincopathological features of Fukuyama type congenital muscular dystrophy (FCMD), a combination of brain malformation and muscular dystrophy with facial muscle and CNS involvement and high prevalence in Japan, are reviewed. Evidence of progressive dystrophy, negative correlations between muscle enzyme levels and age and CT numbers of muscle and age, are presented. Skeletal muscle histopathology is reviewed. Febrile illness-induced transient exacerbation of muscle weakness is reported. Characteristic brain malformations, e.g. micropolygyria, other dysgenesis, are reviewed. Their severity correlated with maximal mental and motor function. The etiology and significance of low density areas (LDA) in white matter on CT, possibly reflecting delayed or abnormal myelination, and ventricular dilatation are discussed. Spontaneous LDA improvement makes hydrocephaly unlikely. Ophthalmological differential diagnosis from Santavouri disease and Walker-Warburg syndrome, characterized by visual disturbance/glaucoma and microphthalmia/anterior chamber defects, respectively, is discussed. A single defective gene, manifesting as a metabolic error, may produce CNS and ocular defects as well as muscle degeneration in FCMD. Key Words Fukuyama type congenital muscular dystrophy, Santavuori disease, Walker-Warburg syndrome, Ophthalmological findings, CNS involvement

Fukuyama type congenital muscular dystrophy (FCMD) [ 1-31 is seldom described outside of Japan, and is characterized by facial muscle and central nervous system (CNS) involvement. It has been attracting attention because of an un-

Received February 22, 1991 Correspondence address: Makiko Osawa, M.D., Department of Pediatrics, Tokyo Women's Medical College, 8-1 Kawadacho, Ichigaya, Shinjuku-ku, Tokyo 162, Japan

usual combination of brain malformation and progressive muscular dystrophy (PMD). Longterm observation of several patients has led us to propose a subclassification based on mental deficiency, the ability to walk and pseudohypertrophy [ 2 , 3 ] .The criterion which differentiated CMD I11 from IV was the absence of pseudohypertrophy. However, we now categorize CMD 111 and IV together because careful review of a series of photos, taken since infancy, does show pseudohypertrophy (Table

262 (1 38) M. Oawa et al. Table 1 . Characteristic features of each subtype of congenital muscular dystrophy treated in our department

Features

Mental defect Head control Ability to walk Pseudohypertophy Elevation of serum CK as compared with normal upper limit Initial joint contracture Fatty replacement of skeletal muscle on CT scan Brain malformation LDA in white matter Round lesion at retina

I (FCMD)

I1 (Non-FCMD) (SevereCMD)

III/IV

V

(Atyp-FCMD) (Benign-FCMD)

++

-

+

++

delayed

delayed

normal

-

-

+--

-

+ ++

delayed -

2 - sx

15 - 80X

10 - 50X hip, knee ankle midcalf > thigh midcalf > paravertebral muscles

pes equinovarus

midcalf f thigh

+

++

+ +

-

+

++ +

-?

X: times

1). The characteristic features of CMD are summarized here.

Findings suggesting progressive muscular dystrophy Facial muscle involvement Facial muscle involvement often produces marked changes in appearance with age. Fig. 1 illustrates the progressive changes in a CMD I patient from infancy through 7 . 5 ~ .Note the rounded, hypertrophic cheeks which are smooth, shiny and firm, before age 3. They subsequently become atrophic and prognathism develops. A tendency to keep the mouth partially open is noticeable from infancy. The upper lip resembles an inverted V while the lower is everted, making it appear rather thick. Unlike normal infants, who close their eyes tightly and open their mouths widely when crying, in CMD I the eyes are slightly open and only the upper lipsmove when crying. A similar, though slower, course of facial involvement appears in CMD III/IV.

Body growth In a study of growth patterns in 75 CMD I and 14 CMD III/IV (6) patients followed for one to 17 years, growth was found to be more severely affected in CMD I. Serial data demonstrated reductions in growth parameters, with the following order of severity: chest circumference, head circumference, height and weight. Longitudinally based height and weight velocity curves for eight children with either CMD I or III/IV indicated a brief acceleration in weight gain, earlier than normal, attributable to an imbalance between mobility and intake, especially in CMD I. Maximum height velocity was more severely reduced than that of weight as compared with normal data. Motor function Delayed motor development usually manifested itself before 6m. CNS development and slow progression of dystrophic change in muscle permit limited improvement in motor function. Peak function, sliding on the buttocks while sitting by extending and flexing the knees with hip rotation (previously termed shuffling) or crawling in CMD 1 and I1 and limited ambu-

Acta Paediarr Jpn

Fukuyama type congenital muscular dystrophy (1 39) 263

Fig. 1: Change of facial appearance

lation in CMD III/IV, was seen between 2y and 8y [2,3] . These functional levels (Ueda) were attained significantly earlier in CMD III/IV than I. No patient’s motor function improved after age 6 but deteriorated. Joint contractures No joint contractures were found at birth. Hip, knee and ankle contractures appeared before age one in CMD I and pes equinovarus around 5y to 8y in IIIIIV. By lOy, contractures of all joints except the shoulder had developed. Serum enzyme activities In CMD I and III/IV, the level of serum CK was 10-50 times higher than normal and decreased after age 7. In CMD I1 it was only 2-5 times higher. We studied the relation between patient age and serum GOT, GPT, LDH, and CK activities in CMD I (68 cases, aged 4m to 17y), I1 (2 cases, 4m to 17y), III/IV (11 cases, 6m to 2 1S y ) [7] . In addition, enzyme activity is generally higher in III/IV. One of us (Ikenaka) [7] found a negative correlation between enzyme value and age: In CMD I: GOT = 93.41 - 4.82 x age (years), r = -0.459, GPT = 64.86 2.80 x age, r = -0.30, LDH = 902.29 - 36.83

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xage, r = -0.364, CK= 3723.55 - 232.19 x age, r = -0.470 (p