American Journal of Medical Genetics 80:288–290 (1998)
Letter to the Editor Another Observation of Langer-Type Sponastrime Dysplasia Variant To the Editor: Sponastrime dysplasia is an autosomal recessive skeletal dysplasia, characterized by osteopathia striata-like metaphyseal modifications and platyspondyly, along with severe mid-face hypoplasia [Fanconi et al., 1983; Lachman et al., 1989]. Comprehensive reviews of this entity have been made recently by Langer et al. [1996; 1997]. In these articles, Langer mentioned his personal experience of six cases with a hitherto undefined skeletal dysplasia that was superficially similar to, but apparently discriminative from, sponastrime dysplasia. However, Langer illustrated only the radiographic finding of one case without detailed description on the clinical manifestations in his articles. In addition to his six cases, there have been two other reports on this disorder, i.e., Langer-type sponastrime dysplasia variant (LSD), in which the patients were regarded as atypical examples of sponastrime dysplasia [Camera et al., 1994; Masuno et al., 1996], and a case of ‘‘tapetoretinal degeneration associated with multisystem abnormalities’’ reported by Liberfarb et al.  probably represents the same entity. We recently encountered a girl with LSD and report her manifestations here to aid in the thorough elucidation of this disorder. The patient was a Japanese girl, the first child of healthy, nonconsanguineous 24-year-old father and 22year-old mother. A maternal uncle had died of cardiomyopathy at age 22 years. The patient was vaginally delivered at 39 weeks’ gestation after an unremarkable pregnancy. Birth length was 49.0 cm (+0.1 SD) and weight 2,806 g (−0.7 SD). Cognitive and communication development was normal, whereas motor development was mildly retarded: she rolled over at 6 months of age, sat up unaided at 8 months, crawled at 15 months, and walked independently at 18 months. Subsequently, however, motor development gradually caught up. At age 13 months, height was 67.5 cm (−2.8 SD), weight 7,685 g (−1.4 SD), and OFC 43.1 cm (−1.4 SD). Mild muscular hypotonia was noted. Serum cre-
*Correspondence to: Gen Nishimura, M.D., Department of Radiology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga-gun, Tochigi-ken 321-02 Japan. E-mail: [email protected]
Received 6 April 1998; Accepted 21 July 1998
© 1998 Wiley-Liss, Inc.
atine kinase level was slightly increased (340 U/L, normal ⳱ 5 to 130 U/L). Flat feet condition was noticed at age 2 years. She was referred to us because of short stature at age 6 3/12 years. Height was 100.7 cm (−2.9 SD), weight 16.0 kg (−1.4 SD), and OFC 48.2 cm (−1.9 SD). Mild micromelia, exaggeration of lumbosacral lordosis, and genu valgum were evident. Craniofacial abnormalities comprised mid-face recession with frontal bossing, a wide nose, and prominent ears (Fig. 1A). She was mentally normal and complained of knee pain. No muscular weakness or muscular hypotonia was evident. Laboratory examinations were unremarkable other than increased serum creatine kinase (430 U/L). Chromosome analysis showed a normal karyotype. Cardiac evaluation, including cardiac ultrasonography, was unremarkable. Skeletal survey at age 6 3/12 years demonstrated posterior scalloping of the lumbar vertebral bodies, interpediculate distance narrowing of the lower lumbar spine, coxa valga with mild constriction of the proximal femora, longitudinal radiodense striations and transverse radiodensities with minor irregularities of the metaphyses in the knee and wrist, and mild epiphyseal flattening of the hip and knee, particularly of the latter (Fig. 1B–D). The carpal and phalangeal skeletal ages were markedly retarded with ivory epiphyses, and the metacarpals were slender (Fig. 1D). At 7 10/12 years, height was 107.0 cm (−3.3 SD) and weight 19.0 kg (−1.4 SD). Genu recurvatum was found. Based on the four previously described patients [Liberfarb et al., 1986; Camera et al., 1994; Masuno et al., 1996; Langer et al., 1996; 1997] as well as our patient, the clinical hallmarks of LSD comprise severe mid-face hypoplasia, mild retardation of early motor development, and postnatal growth failure with micromelia. The motor developmental delay may be related to muscular hypotonia. The short stature becomes evident in early childhood. The radiological hallmark includes longitudinal radiodense striations with minor irregularities of the metaphyses of the long bones, which were present in mid-childhood in our patient. Although a combination of these malformations superficially resembles that of sponastrime dysplasia, several skeletal alterations including coxa valga with proximal femoral constriction, mild epiphyseal dysplasia of the long bones particularly in the knee, overtubulation of the metacarpals, and markedly delayed skeletal age of the hand aid in the differential diagno-
Letter to the Editor
Fig. 1. Mid-face hypoplasia at age 7 years (A); coxa valga with mild constriction of the proximal femora (B); metaphyseal irregularities and radiodense striations and flattening of the epiphyses (C); and longitudinal striations in the metaphyses of the distal radii and ulnae, delayed skeletal age, multiple ivory epiphyses, and slender metacarpals (D) at age 6 3/12 years.
sis. Mild modification of the lumbar vertebral bodies in LSD also contrasts with overt platyspondyly in sponastrime dysplasia. The potentially hazardous orthopedic problems in LSD include malalignment of the knee, lumbar canal stenosis, and scoliosis [Camera et al., 1994; Masuno et al., 1996; Liberfarb et al., 1986]. In fact, scoliosis and genu valgum were profound in Liberfarb’s patient, and this patient had pigmentary degeneration of the retina, sensorineural hearing impairment, mental retardation, and susceptibility to airway infection. Subglottic stenosis may be another hazardous complication in LSD, as in sponastrime dysplasia [Langer et al., 1996; Masuno et al., 1996]. Increased creatine kinase values at ages 13 months and 6 years in our patient raise the
possibility that subclinical myopathy is part of the syndrome. LSD should be a single-gene defect, but the mode of inheritance remains unknown because of the sporadic occurrence. X-linked inheritance may be excluded by the occurrence of equal severity in both genders. The clinical phenotype of LSD is too nonspecific to distinguish it from a number of bone dysplasias, therefore the diagnosis rests on the radiographic findings. Based on eight unpublished (Langer LO Jr., personal communication) and 5 published cases [Liberfarb et al., 1986; Camera et al., 1994; Langer et al., 1996; Masuno et al., 1996] including our patient, the radiographic findings are diagnostic between ages 2 years and 4 years. The clinical and radiological variability in this entity will be
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elucidated by additional reports on these unpublished cases.
Masuno M, Nishimura G, Adachi M, Hotsubo T, Tachibana K, Makita Y, Imaizumi K, Kuroki K (1996): SPONASTRIME Dysplasia: Report on a female patient with severe skeletal changes. Am J Med Genet 66:429– 432.
REFERENCES Camera G, Camera A, Pozzolo S, Costa P (1994): Sponastrime dysplasia: Report on a male patient. Pediatr Radiol 24:322–324. Fanconi S, Issler C, Giedion A, Prader A (1983): The SPONASTRIME dysplasia: Familial short-limb dwarfism with saddle nose, spinal alterations and metaphyseal striation. Helv Paediatr Acta 38:267–280. Lachman RS, Stoss H, Spranger J (1989): Sponastrime dysplasia: A radiologic-pathologic correlation. Pediatr Radiol 19:417–424. Langer LO Jr, Beals RK, LaFranchi S, Scott Ci Jr, Sockalosky JJ (1996): Sponastrime dysplasia: Five new cases and review of nine previously published cases. Am J Med Genet 63:20–27. Langer LO Jr, Beals RK, Scott CI Jr (1997): Sponastrime dysplasia: Diagnostic criteria based on five new and six previously published cases. Pediatr Radiol 27:409–414. Liberfarb RM, Katsumi O, Fleischnick E, Shapiro F, Hirose T (1986): Tapetoretinal degeneration associated with multisystem abnormalities. Ophthalmic Paediatr Genet 7:151–158.
Gen Nishimura* Department of Radiology Dokkyo University School of Medicine Tochigi, Japan Makoto Mikawa Department of Pediatrics Kitami Red Cross Hospital Kitami, Japan Yoshimitsu Fukushima Department of Hygiene and Medical Genetics Shinsyu University School of Medicine Matsumoto, Japan