Brief Communications

Nonprogressive Familial Leukoencephalopathy With tation demonstrated a hyperechogenic periventricular lesion that was
Porencephalic Cyst and Focal Seizures shown postnatally to represent a porencephalic cyst. Development was nor-
mal except for mild motor delay secondary to left spastic hemiparesis. The
first signs of hemiparesis appeared at the age of 9 months as functional asym-
ABSTRACT metry of the hands. Lower limb involvement was appreciated at 15 months
when she started walking. There has been no progression of her symptoms
Two siblings with a similar white-matter disease but different clin- and no involvement of the right side. At the age of 7 years, she is a nondys-
morphic girl with symptoms of inattention and hyperactivity. Her head cir-
ical symptoms are described. The first sibling suffers from non-
cumference is normal. She has left spastic hemiparesis without cranial
progressive spastic hemiparesis secondary to a congenital nerve involvement. Coordination is intact. Her speech, language, cognitive
periventricular porencephalic cyst. Her brother has focal epilepsy. functions, and communication skills are age appropriate.
On magnetic resonance imaging, both patients show diffuse white- Brain MRI at 15 months demonstrated T2-weighted hyperintense and
matter involvement predominantly of the posterior periventricu- T1-weighted hypointense lesions predominantly affecting the posterior
region of the periventricular white matter, centrum semiovale, and poste-
lar area. We suggest that this is a familial white-matter disorder with
rior limb of the internal capsule with very mild involvement of the dentate
minimal symptoms and no progression in early childhood. (J Child nucleus. There was sparing of the U fibers and corpus callosum. A right
Neurol 2006;21:145–148; DOI 10.2310/7010.2006.00036). frontal periventricular porencephalic cyst was prominent (Figure 1). There
was neither enhancement nor atrophy. A brainstem auditory evoked response
was normal. Repeat MRI at the age of 6 years showed the same findings.
White-matter abnormalities, although uncommon in the general population, In view of the congenital porencephalic cyst, the patient was evalu-
can be frequently encountered among children with developmental delay ated for a coagulation disorder. All tests were normal. The surprising find-
and neurologic deficits.1 The leukoencephalopathies encompass a hetero- ing of extensive white-matter involvement led to further evaluation that
geneous group of diseases that includes multiple conditions which selec- included routine hematology and chemistry panels, blood amino acids,
tively or predominantly affect the white matter of the brain.2 The term serum lactate, pyruvate, very-long-chain fatty acids, phytanic acid, lysoso-
“leukoencephalopathy” is broader than the term “leukodystrophy” and is mal enzyme activity (arylsulfatase A, galactocerebrosidase, hexosaminidase),
not restricted to inherited diseases that affect myelin development. Leukoen- and urinary organic acids. All tests were normal.
cephalopathy is the preferred term for describing diseases with either pri- Her family history is significant for childhood-onset schizophrenia in
mary or secondary changes in myelin development or maintenance.3 a maternal uncle. A brother, now 5 years old, was born with an omphalo-
Leukoencephalopathies can be congenital (inherited or sporadic) or cele that was successfully repaired. He suffers from developmental language
acquired. There can be isolated white-matter involvement, and the leukoen- delay without hearing impairment. A brain MRI was not obtained owing to
cephalopathy can be part of a genetic syndrome or associated with a con- parental objection.
genital myopathy, such as congenital muscular dystrophy4 and myotonic
dystrophy.5 In some cases, the clinical course of the disease and the neu- Case 2
roimaging findings allow for an early diagnosis of a specific disease. In oth- The youngest sibling presented with partial seizures at the age of 11 months.
ers, the etiology of the leukoencephalopathy remains unclear even after a He was born after a normal pregnancy and an uneventful delivery. Psy-
comprehensive investigation. chomotor development was normal except for asymmetric gait and left arm
There are different classifications of white-matter disorders that try dominance at age 10 months and a mild delay in expressive language.
to combine pathology, biochemistry, and genetics.3 However, these classi- Seizures were simple partial, beginning with eye deviation to the right and
fications might not be helpful when dealing with the large group of unclas- clonic movements on the right side. Neurologic and developmental exam-
sified leukoencephalopathies. Although our knowledge of the etiology and ination at the age of 20 months revealed drooling, mild asymmetry in fine
pathogenesis of diseases with white-matter involvement is constantly grow- motor functions, and expressive language delay. A repeat electroen-
ing, many disorders remain undiagnosed, especially in the early stages of cephalographic study revealed a left frontocentral epileptogenic focus.
the disease. The diagnostic yield can be improved by categorizing white- Brain MRI was performed at age 18 months and demonstrated the same
matter disorders based on pattern recognition on magnetic resonance white-matter lesions as his sister’s (Figure 2) but no porencephalic cyst. Mag-
imaging (MRI).6 Beyond facilitating the classification of white-matter netic resonance spectrography was normal. He was treated with sodium val-
involvement into seven major subgroups,1 it has prompted the recognition proate without significant improvement. Complete seizure control was
of multiple new white-matter disorders. achieved with carbamazepine. An MRI a year later did not show progres-
We describe a family with at least two members with similar, non- sion of his white-matter involvement.
progressive white-matter lesions on brain MRI and few neurologic signs. A
systematic analysis ruled out metabolic leukodystrophies. The pattern of
Discussion
white-matter involvement is consistent with category D of van der Knaap’s
The etiology of over half of all pediatric cases with white-matter disease
categorization.1 We suggest that this is a familial leukoencephalopathy with
remains unknown despite a methodic clinical and laboratory evaluation6–8
minimal symptomatology in early childhood.
that includes screening for inborn errors of metabolism of amino acids,
organic acids, cholesterol, peroxisomal disorders, lysosomal diseases, mito-
chondrial disorders, chromosomal analysis, and immune-mediated and
Case Reports infectious central nervous system disorders. With no clear etiology for the
leukoencephalopathy, the chances of offering specific treatment and of deter-
Case 1 mining the prognosis for an individual patient or of providing prenatal
The patient is a 7-year-old girl, the product of a spontaneous pregnancy and diagnosis to the parents are markedly reduced.1
normal delivery. The parents are healthy nonconsanguineous Sephardic Jews Kristjansdottir et al investigated 26 children with white-matter abnor-
from Yemenite and Syrian origin. Fetal ultrasonography at 23 weeks’ ges- malities of unknown origin in an attempt to find diagnostic clues.8 The diag-

145
146 Journal of Child Neurology / Volume 21, Number 2, February 2006

Figure 2. Axial fluid-attenuated inversion recovery image demonstrates

Figure 1. Axial T2-weighted image at the level of the centrum semio- high signal foci within the periventricular white matter bilaterally and
vale demonstrates a right porencephalic cyst surrounded by diffuse in the left posterior limb of the internal capsule.
white-matter changes.

affects periventricular white matter. It is unclear whether the porencephalic

nosis was eventually made in six cases: Salla disease, infantile neuroax- cyst in case 1 is a prenatal manifestation of the white-matter disease or results
onal dystrophy, cytochrome c oxidase deficiency, Alpers disease, Angel- from an ischemic event unrelated to it. The causal relationship between the
man syndrome, and muscle-eye-brain disease. All children with onset of focal seizures and the diffuse white-matter involvement in case 2 is also
symptoms after 18 months of age had a progressive disease. Affected sib- unclear. However, seizures are frequently seen in patients with periventricular
lings were more common when a progressive disorder was present. Pre- leukomalacia.13
natal stigmata were present only in children with nonprogressive disorders. Megalencephalic leukoencephalopathy with subcortical cysts is a
Siblings often had similar MRI findings and a similar disease course with new clinically and genetically defined disorder that is characterized by
a variable age at onset, severity of clinical features, and extension of craniomegaly from infancy, progressive spasticity and ataxia, and an exten-
white-matter abnormalities.8 sive symmetric white-matter disorder with relative sparing of the deeper
van der Knaap et al evaluated 277 patients whose MRI showed lesions structures and subcortical cysts.14 The disorder is caused by an autosomal
located exclusively or predominantly in the white matter to develop a cat- recessive mutation in the MLC1 gene. Although several genotypic and phe-
egorization scheme according to pattern recognition.6 The diagnosis notypic variations have been described and not all cases are associated with
remained unknown in 48 cases. a large head, we do not find similarity to the disorder in our patients
Using this magnetic resonance pattern recognition approach in cases because of the prenatal appearance of a porencephalic cyst in the first case,
of leukoencephalopathy of unknown origin, homogeneous subgroups of a nonprogressive course, and a lack of neurologic signs, such as ataxia and
affected patients could be discerned.1 This led to the definition of four spasticity in both siblings. The MRI findings are also different. This disor-
new nosologic entities (with subsequent determination of the genetic basis der has been described in Israel in Libyan Jews with the classic clinical pre-
of two of them): megalencephalic leukoencephalopathy with subcortical sentation.15
cysts,9 vanishing white-matter disease/childhood ataxia with central nervous The clinical and radiologic features in these two siblings are quite rem-
system hypomyelination,10 leukoencephalopathy with brainstem and spinal iniscent of hereditary porencephaly described by Mancini et al.16 The
cord involvement and high lactate,11 and congenital cytomegalovirus infec- authors report on two unrelated families with apparent dominantly inher-
tion with white-matter involvement.12 ited porencephaly and white-matter involvement with motor impairment,
The MRI findings in our two siblings meet the criteria for category D hemiplegia, mental retardation, and epilepsy. Although white-matter disease
according to van der Knaap et al’s classification of leukoencephalopathies1: was present in all cases, not all patients had porencephalic cysts. However,
predominance of periventricular white-matter abnormalities, arcuate fiber in the few cases with no cyst, white-matter involvement was rather restricted
sparing, corpus callosum and internal capsule involvement with the pos- to the periventricular area. Whether our patients suffer from the same con-
terior limb more often than the anterior limb, and symmetry of findings. The dition remains to be established inasmuch as the white-matter lesions in the
patients in category D usually had a progressive course, but some showed two siblings spread over larger areas than those seen in the report by
a static one. Periventricular white-matter involvement with arcuate fiber spar- Mancini et al.
ing is typical of metachromatic leukodystrophy, Krabbe disease, and X-linked White-matter changes can be seen in the presymptomatic stage of van-
adrenoleukodystrophy,1 all of which were ruled out in our patients. Further ishing white-matter disease, one of the most prevalent inherited child-
laboratory investigations ruled out other known metabolic causes. Acquired hood leukoencephalopathies.10 This disorder can begin in infancy or even
leukoencephalopathies (owing to prenatal ischemia) were discarded in antenatally,17 is caused by mutations in any of five eIF2B genes,18 and is
view of the similar pattern of white-matter involvement in both siblings. Con- inherited in an autosomal recessive mode. The disorder is characterized
genital cytomegalovirus infection was excluded by negative serology in the by episodes of rapid neurologic deterioration often following febrile ill-
mother. nesses. Most patients have normal initial development. In cases of earlier
Our patients can either suffer from a slow or nonprogressive illness or antenatal onset, the patients had severe neurologic disabilities and died
or a presymptomatic stage of a leukoencephalopathy that predominantly during the first months or years.17,19 Brain MRI shows diffuse cerebral
 Brief Communications 147

white-matter abnormalities and evidence of rarefaction and cystic degen- Gustavo Malinger, MD
eration of the abnormal white matter. This disorder can be ruled out in our Prenatal Neurology Clinic
patients since white-matter involvement is already more extensive in Wolfson Medical Center
presymptomatic MRI studies of patients with vanishing white matter, and Holon, Israel
the lesions always extend beyond the periventricular regions.18 In the Yehudit Luckman, MD
older sibling, the clinical picture reflects the prenatal porencephalic cyst Radiology Department
with no subsequent neurologic deterioration, neuroimaging progression, Wolfson Medical Center
or other organ involvement during 7 years. The younger brother showed Holon, Israel
mild, well-controlled partial epilepsy during a 2-year- period with no exten- Bruria Ben-Zeev, MD
sion of white-matter lesions. So the clinical and neuroimaging phenotype Pediatric Neurology Unit
of both patients is different from the known cases of antenatal or early onset Sheba Medical Center
of eIF2B-related disorders.17,19 Ramat-Gan, Israel
A periventricular leukoencephalopathy consistent with pattern D has Tally Lerman-Sagie, MD
been described in the presymptomatic stage of an autosomal dominant Pediatric Neurology Unit
leukoencephalopathy with adult onset (40–50 years).20 However, none of Metabolic-Neurogenetic Clinc
these patients were studied in childhood. The earliest MRI was obtained at Prenatal Neurology Clinic
the age of 36 years, only a few years before the usual onset of symptoms Wolfson Medical Center
in this disorder. The MRI changes were progressive from the asympto- Holon, Israel
matic to the symptomatic stage. Therefore, it is extremely unlikely that our
patients have the same disorder. Received February 15, 2005. Received revised March 18, 2005. Accepted
White-matter abnormalities can be seen in the presymptomatic stage for publication March 31, 2005.
of another autosomal dominant disorder with white-matter involvement: cere- Address correspondence to Dr Tally Lerman-Sagie, Pediatric Neurology
bral autosomal dominant arteriopathy with subcortical infarcts and leukoen- Unit, Wolfson Medical Center, Holon, Israel 58100. Tel: 972-3-5028458; fax:
cephalopathy (CADASIL). This disorder usually presents with strokes, 972-3-5028141; e-mail: [email protected].
transient ischemic attacks, or migraine. Rarely, chronic depression, cogni-
tive impairment, or epilepsy are the initial manifestations of the disease.21 References
Although usually a disease of middle adulthood, childhood onset has been 1. van der Knaap MS, Breiter SN, Naidu S, et al: Definition and catego-
described.22 Moreover, a subclinical stage is not uncommon in cerebral rizing leukoencephalopathies of unknown origin: MR imaging approach.
autosomal dominant arteriopathy with subcortical infarcts and leukoen- Radiology 1999;213:121–133.
cephalopathy.23,24 However, there are no reports describing intrauterine or 2. van der Knaap MS: Magnetic resonance in childhood white-matter dis-
infantile onset of cerebral autosomal dominant arteriopathy with subcor- orders. Dev Med Child Neurol 2001;43:705–712.
tical infarcts and leukoencephalopathy. Hence, cerebral autosomal domi- 3. Kaye EM: Update on genetic disorders affecting white matter. Pedi-
nant arteriopathy with subcortical infarcts and leukoencephalopathy is atr Neurol 2001;24:11–24.
probably an unlikely explanation for the clinical picture of our patients with 4. van der Knaap MS, Smith LM, Barth PG, et al: Magnetic resonance imag-
a prenatal onset and nonprogressive symptoms. ing in classification of congenital muscular dystrophies with brain
Asymptomatic white-matter involvement has been described in another abnormalities. Ann Neurol 1997;42:50–59.
rare autosomal dominant disorder: familial leukoencephalopathy in bipo- 5. Di Costanzo A, Di Salle F, Santoro L, et al: Brain MRI features of con-
lar disorder.25 Fifteen of 21 family members had MRI findings, including 6 genital- and adult-form myotonic dystrophy type 1: Case-control study.
of 10 unaffected members. These findings included deep white-matter Neuromuscul Disord 2002;12:476–483.
changes and lesions in subcortical gray nuclei. Our patients have an uncle 6. van der Knaap MS, Valk J, de Neeling N, Nauta JJP: Pattern recogni-
with a psychiatric illness. Unfortunately, he refused to undergo an MRI study. tion in magnetic resonance imaging of white matter disorders in chil-
Hence, we could not establish whether there is any relationship between dren and young adults. Neuroradiology 1991;33:478–493.
his disease and that of our patients. 7. Kristjansdottir R, Uvebrant P, Hagberg B, et al: Disorders of the cere-
In summary, we report on two siblings with a static condition char- bral white matter in children. The spectrum of lesions. Neuropediatrics
acterized by minimal motor compromise in the presence of diffuse white- 1996;27:295–298.
matter disease. The oldest child also has a right porencephalic cyst with 8. Kristjansdottir R, Uvebrant P, Wiklund L-M: Clinical characteristics of
corresponding left hemiplegia but minimal motor signs on the right side of children with cerebral white matter abnormalities. Eur J Paediatr Neu-
her body. The younger patient also has partial seizures despite the widespread rol 2000;4:17–26.
white-matter involvement. These two cases bear a resemblance to the two 9. van der Knaap MS, Barth PG, Stroink H, et al: Leukoencephalopathy
families recently reported with hereditary porencephaly and white-matter with swelling and a discrepantly mild clinical course in eight children.
disease. However, our patients’ MRI studies depict a greater extension of Ann Neurol 1995;37:324–334.
the white-matter lesions. Therefore, whether these two siblings suffer from 10. van der Knaap MS, Barth PG, Gabreels FJ, et al: A new leukoen-
a distinct clinical entity or are part of the spectrum of hereditary porencephaly cephalopathy with vanishing white matter. Neurology 1997;48:845–855.
remains to be seen. 11. van der Knaap MS, van der Voorn P, Barkhof F, et al: A new leukoen-
cephalopathy with brainstem and spinal cord involvement and high
lactate. Ann Neurol 2003;53:252–258.
12. van der Knaap MS, Vermeulen G, Barkhof F, et al: Pattern of white mat-
Lubov Blumkin, MD
ter abnormalities at MR imaging: Use of polymerase chain reaction test-
Nathan Watemberg, MD ing of Guthrie cards to link pattern with congenital cytomegalovirus
Pediatric Neurology Unit infection. Radiology 2004;230:529–536.
Metabolic-Neurogenetic Clinic 13. Gurses C, Gross DW, Andermann F, et al: Periventricular leukomala-
Wolfson Medical Center cia and epilepsy: Incidence and seizure pattern. Neurology
Holon, Israel 1999;52:341–345.
Dorit Lev, MD 14. Singhal BS, Gorospe JR, Sakkubai N: Megalencephalic leukoen-
Metabolic-Neurogenetic Clinic cephalopathy with subcortical cysts. J Child Neurol 2003;18:646–652.
Genetics Institute 15. Ben-Zeev B, Levy-Nissenbaum E, Lahat H, et al: Megalencephalic
Prenatal Neurology Clinic leukoencephalopathy with subcortical cysts; a founder effect in Israeli
Wolfson Medical Center patients and a higher than expected carrier rate among Libyan Jews.
Holon, Israel Hum Genet 2002;111:214–218.
148 Journal of Child Neurology / Volume 21, Number 2, February 2006

16. Mancini GMS, de Coo IFM, Lequin MH, Arts WF: Hereditary poren- ferent gene mutations. Epilepsy is seen in Fukuyama-type congenital mus-
cephaly: Clinical and MRI findings in two Dutch families. Eur J Pae- cular dystrophy because of neuronal migration defects in the brain.1 We report
diatr Neurol 2004; 8:45–54. a boy with Duchenne muscular dystrophy and generalized convulsive
17. van der Knaap MS, van Berkel CGM, Herms J, et al: eIF2B-related dis- epilepsy with normal brain magnetic resonance imaging (MRI) and another
orders: Antenatal onset and involvement of multiple organs. Am J Hum boy with absence epilepsy, normal brain MRI, and autosomal recessive
Genet 2003;73:1199–1207. limb-girdle muscular dystrophy with partial calpain deficiency. We also
18. van der Knaap MS, Leegwater PA, Konst AA, et al: Mutations in each review coexisting muscular dystrophies with epilepsy in children.
of the five subunits of translocation initiation factor eIF2B can cause
leukoencephalopathy with vanishing white matter. Ann Neurol
2002;51:264–270. Case 1
19. Folgi A, Dionisi-Vici C, Deodato F, et al: A severe variant of childhood This 12-year-old boy was born at term by emergency cesarean section for
ataxia with central hypomyelination/vanishing white matter leukoen- placenta previa, weighing 9 pounds and 12 ounces, without postnatal prob-
cephalopathy related to EIF21B5 mutation. Neurology 2002;59: lems. He walked at 1 year but had always been slower than other children
1966–1968. and needed to hold on to the side rails to go up and down stairs since age
20. Bergui M, Bradac GB, Leombruni S, et al: MRI and CT in an autoso- 3 years. He was easily tired, and his legs hurt intermittently after walking
mal-dominant adult-onset leukodystrophy. Neuroradiology for a few blocks. His serum creatine kinase level was 9868 U/L (normal 37–
1997;39:423–426. 430 U/L) at age 9 years. The physical and neurologic examinations were nor-
21. Desmond DW, Moroney JT, Lynch T, et al: The natural history of mal except for mild proximal muscle weakness in all four extremities and
CADASIL. A pooled analysis of previously published cases. Stroke hypertrophy of both calf muscles. The muscle biopsy revealed marked
1999;30:1230–1233. fiber size variability, foci of fiber regeneration, and endomysial fibrosis, con-
22. Kotorii S, Sakae N, Yamada N, et al: A case of CADASIL in early stage. sistent with muscular dystrophy. Immunostaining studies were normal for
Rinsho Shinkeigaku 2001;41:306–309. dystrophin, ␣- and ␥-sarcoglycans, laminin ␣2, and ␤-dystroglycan. However,
23. Skehan SJ, Hutchinson M, MacErlaine DP: Cerebral autosomal dom- muscle Western blotting demonstrated partial calpain deficiency. A leuko-
inant arteriopathy with subcortical infarcts and leukoencephalopathy: cyte dystrophin gene mutation study was also normal. On follow-up neu-
MR findings. AJNR Am J Neuroradiol 1995;16:2115–2119. rologic examination at age 12 years 9 months, he had mild proximal muscle
24. Coulthard A, Blank SC, Bushby K, et al: Distribution of cranial MRI weakness and atrophy in the four extremities and shoulder and pelvic gir-
abnormalities in patients with symptomatic and subclinical CADASIL. dle muscles.
Br J Radiol 2000;73:256–265. He started to say single words prior to age 1 year but has always had
25. Ahearn EP, Steffens DC, Cassidy F, et al: Familial leukoencephalopa- misarticulation, requiring speech therapy. He also has learning difficulties
thy in bipolar disorder. Am J Psychiatry 1998;155:1605–1607. and is attending a special learning disability class. He developed absence
epilepsy with 3-hertz generalized spike-and-wave discharges at age 7 years,
which has been completely controlled by ethosuximide for 3 years. His brain
MRI was normal at age 9 years.
Coexisting Muscular Dystrophies His family history is significant for limb-girdle muscular dystrophy in
and Epilepsy in Children a 25-year-old sister, and another 19-year-old sister also has similar muscle
weakness. However, there is no epilepsy in the family.

ABSTRACT
Case 2
This 9-year-old boy was seen for recurrent generalized tonic-clonic seizures
Muscular dystrophies are composed of a variety of genetic mus-
and difficulty going up and down stairs. He was born at term by forceps vagi-
cle disorders linked to different chromosomes and loci and asso- nal delivery. He had hypotonia, apnea, and neonatal seizures at birth, and
ciated with different gene mutations that lead to progressive muscle he had been treated with phenobarbital since then. He rolled over at 9
atrophy and weakness. Fukuyama congenital muscular dystrophy months, sat at 14 months, began walking awkwardly at 2¹⁄₂ years, could never
is frequently associated with partial and generalized epilepsy and run, and always had problems going upstairs. He was always clumsy and
could not keep up with his classmates during exercise. He also had mild
congenital brain anomalies, including cobblestone complex and
mental retardation. His family history is positive for epilepsy in a maternal
other neuronal migration defects. We report generalized convul- uncle; however, his parents, 11-year-old brother, 6-year-old and 5-year-old
sive epilepsy in a boy with normal brain magnetic resonance imag- sisters, and other family members did not have epilepsy or neurologic or
ing and Duchenne muscular dystrophy with deletion of dystrophin neuromuscular disorders.
gene, and we report absence epilepsy with normal brain magnetic Physical and neurologic examinations revealed proximal muscle
weakness in the upper and lower extremities, calf muscle hypertrophy, lor-
resonance imaging in another boy with limb girdle muscular dys-
dotic gait, and mild ankle tightness. Brain MRI was normal. The serum cre-
trophy with partial calpain deficiency. We, therefore, review coex- atine kinase level was 9900 U/L (normal 0–235 U/L). Electromyography
isting musclar dystrophies and epilepsy in children. In addition to revealed myopathic features. Quadriceps muscle biopsy showed a dys-
Fukuyama congenital muscular dystrophy, partial or generalized trophic process consisting of necrosis and regeneration of muscle fibers and
epilepsy has also been reported in the following types of muscu- increased endomysial connective tissues. The muscle biopsy was stained
for dystrophin and found to be completely deficient, consistent with
lar dystrophies, including Duchenne/Becker dystrophy, facioscapu-
Duchenne muscular dystrophy. Deletion of exons 46 to 52 was detected by
lohumeral dystrophy, congenital muscular dystrophy with partial blood dystrophin gene mutation study. His seizures were completely con-
and complete deficiency of laminin ␣2 (merosin) chain, and limb trolled with sodium valproate.
girdle muscular dystrophy with partial calpain deficiency. (J Child
Neurol 2006;21:148–150; DOI 10.2310/7010.2006.00035). Discussion
Duchenne muscular dystrophy is the most common muscular dystrophy,
occurring in 1 in 3500 live male infants.2 Becker muscular dystrophy is an
allelic disorder of Duchenne muscular dystrophy but occurs much less fre-
quently. They are caused by dystrophin gene mutations, with 65% of cases
Muscular dystrophies are heterogeneous groups of inherited muscle dis- from large deletions, 5% of cases from duplications, and the remaining
orders with progressive muscle wasting and weakness associated with dif- cases owing to small private and random mutations.3 About 20% of boys