Osteopathia striata with cranial sclerosis B. B. Gay, JF. 1, L.J. Elsas 2, J. B. Wyly 1, M. Pasquali 2 Department of Radiology, Pediatric Section, Emory University School of Medicine and the Egleston Children's Hospital at Emory University, Atlanta, Georgia, USA 2 Department of Pediatrics, Genetics Section, Emory University School of Medicine and the Egleston Children's Hospital at Emory University, Atlanta, Georgia, USA Received: 9 July 1993/Accepted: 3 September 1993
Abstract. Osteopathia striata with cranial sclerosis (OSCS) is a specific bone dysplasia manifested by hypertelorism, fiat nasal bridge, frontal bossing, large head, hypoplastic maxilla, palate anomalies, chronic otitis media, hearing deficits, nasal obstruction, and neurological changes of deafness, facial palsy, ophthalmoplegia, and mental retardation. We will review the clinical and radiologic findings in a new patient from birth to 20 years; this is believed to be the thirty-fifth patient reported. OS-CS is 2.5 times more common in females and occurs as an autosomal dominant condition or a sporadic dominant mutation with patients presenting for evaluation from the newborn period to the fifth decade. Skeletal abnormalities are distinctive including sclerosis of the skull base and calvarium, linear striated densities in the long bones and pelvis, and poor development of the mastoid and sinus air cells. Radionuclide bone scans with SPECT indicated in our patient increased bone turnover which was supported by biochemical findings of increased pyridinoline excretion. The major complications are due to constriction of essential foramina at the skull base. The condition is not lifethreatening but can produce disability.
Materials and methods The clinical and radiologic records were reviewed. Pyridinoline (Pyr) and deoxy-pyridinoline (DPyr) determinations were measured in the urine of our patient at 20 years of age. Pyridinolines are stable products of bone-collagen degradation and are sensitive markers of bone resorption [8, 9]. These metabolites were quantitated using high performance liquid chromatography (HPLC) separation and crystallized standards (courtesy of Merck, Sharp, and Dohme Research Laboratories) in normal sex-and-age-matched controls and compared to that excreted by our patient (Table 1). Values obtained in the control group were comparable to those previously reported . Also at 20 years age, a bone scan with single photon emission computed tomography (SPECT) was performed after intravenous injection of 18.0 millicuries (666 milliBecquerels) of Technetium99m Methylene Diphosplionate (MDP) with tow energy, all-purpose collimator on single crystal gamma camera. The literature concerning osteopathia striata with cranial sclerosis was reviewed.
Clinical features of patient Osteopathia striata (OS) was named by Fairbank in 1935  after being described by Voorhoeve in 1924 . Hurt in 1953  noted cranial sclerosis in association with osteopathia striata (OS-CS). OS without cranial condensation may occur as an isolated lesion [4, 5] or with other conditions [4, 6, 7]. The present report describes the clinical course and radiologic findings, from birth to 20 years, of a new patient having OS-CS with the addition of urinary pyridinoline excretion determinations for bone metabolism, single photon emission computed tomography (SPECT) of skull, and a review of the literature. Presented at the first meeting of The Bone Dyplasia Society at the Children's Memorial Hospital, Chicago, Illinois, USA, May 18, 1993
Correspondence to: B.B. Gay, Jr., MD, Department of Radiology, Egleston Children's Hospital at Emory University, 1405 Clifton Road, N. E., Atlanta, Georgia 30322, USA
This white, female, newborn full-term infant was transferred at i day age from another hospital because of severe respiratory distress with stridor, cyanosis, low-set ears, and high-arched palate. The patient was treated in the intensive care unit because of severe respiratory distress. H e r course was complicated by beta Streptococcus sepsis, stridor, and laryngomalacia and required gastrostomy and tracheostomy. The patient was discharged home at 69 days of age. During the next few months the patient had recurrent otitis media, nasal obstruction, and respiratory infections. At 32/12years, examination of the nasopharynx under general anesthesia revealed the choanae to be very stenotic. Adenoid tissue was removed to enlarge the nasopharynx. The epiglottis was small. Ventilation tubes were inserted through the tympanic membranes bilaterally after removal of thick fluid of high viscosity from the middle ear.
Pyr = Pyridinoline; Cr = Creatinine; DPyr = Deoxypyridinoline. a The DPyr/Pyr ratio does not change with age whereas Pyr excretion decreases with age. The ratio of 18 in our patient is low and suggests increased Pyr urinary excretion secondary to increased bone turnover At 34/12 years corrective surgery for exotropia (3rd nerve deficiency) was performed. At 36/12years hearing loss was 30-35 decibels. The patient had clinical reevaluation by the Genetics Service at 37/12years age. Positive physical findings were: large head (circumference 54.6 cm and greater than 98 percentile) with biparietal and occipital bossing, midface hypoplasia, anterior fontanelle 7 x 10 cm, myringotomy tubes bilaterally, hypertelorism with epicanthal folds, synophrys and persistent exotropia, minimal clouding of the lens bilaterally, high arched palate, and delayed dentition. Only the patient was affected and there was no history of consanguinity. At 13 years age the patient had tympanoplasty and mastoidectomy and ossicular chain reconstruction with prosthesis. The patient was seen in the Genetics Clinic at age 19 years. She had adjusted well socially, completing high school and attending first year of college. The positive clinical findings were: height 156 cm (25th percentile), head circumference 61.5 cm (above 98th percentile), superior and medial deviation of the left eye on right lateral gaze (3rd nerve deficiency), dental braces, hearing aids bilaterally, midfacial hypoplasia, loss of "sweet" taste on left side of tongue (12th nerve deficiency).
Pyridinoline excretion study Our patient excreted in the urine significantly increased amounts of Pyr but not DPyr giving an abnormally low DPyr/Pyr ratio (Table 1). This finding is consistent with increased bone turnover.
Radiologic examinations During the first month of life, chest radiographs showed the clavicles, ribs, and scapulae to be very dense. The medial and lateral ends of the clavicles were broadened. The left femur was dense with no linear striations visualized; the distal femoral and proximal tibial epiphyses were not present (Fig. 1). Minimal linear, opaque, striations in the metaphyses of the proximal humeri (Fig. 2) appeared at one month of age and became more prominent at 10 months age. The vertebrae had a normal infantile pattern. The ilium showed faint linear striated densities.
Linear tomography of the facial bones at 32/12years showed a midline cleft of the hard palate, hypertelorism, and underdevelopment of the maxillary sinuses. At 36/12years age dense linear striations in the femoral necks and epiphyses, and minimal striations in the pelvic bones were present. The lower extremities showed minimal, course, dense, linear striations in the distal diaphysis, metaphysis, and epiphysis of the femurs and tibias bilaterally. The distal tibial epiphysis was very small. Faint striations were present in the fibular shaft proximally and distally. Linear striations were present in the shafts of the first metatarsal and proximal phalangeal bones bilaterally, and in the distal half of the radius and proximal ulna. The spine was normal. There was decreased bone maturation (bone age 11/2 years by Greulich and Pyle standards  compared to chronologic age of 3Z/2years). The skull was dense in base, frontal, and occipital areas. The calvarium was large and measured 4 mm in thickness. The angle of the mandible was obtuse. Slight striated densities were present in the ascending rami with course, linear trabeculae in the body of the mandible. The mastoid areas were dense. The sinuses were small. Computed tomography of the head at 37/12 and 3 8/12 years showed mild ventricular dilatation and increased density and thickening of the calvarium and skull base. At 8 years age the linear, striated densities in all of the bones (Fig. 4, 5) were more prominent than earlier. The paranasal sinuses were small and the facial bones were dense. The calvarium measured 8 mm in thickness with increased sclerosis of the skull base, mastoid areas, and facial bones (Fig. 3). At 19 years of age the clavicles were short, broad, and dense with cortical thickening in the middle third of the diaphysis and broadening of the medial thirds. The ribs were broad posteriorly with minimal trabecular striation parallel to the cortex. Dense striations were present in the proximal humeral shaft. Twelve ribs were present. There was slight thoracolumbar scoliosis. The calvarium now measured 22 mm in thickness (Fig.6). The facial bones were dense with little air content in the sinuses. The mandible was dense with a persisting obtuse mandibular angle. Dense striations continued in the femurs and tibias; the growth plates had closed (Fig. 7). At 20 years age the skull was unchanged. Radiographs of the skull and long bones were obtained on the patient's parents. These studies showed no evidence of bone abnormality.
SPECTimaging Images showed increased uptake of tracer activity within the calvarium, mid-face, skull base, and mandible (Fig. 8), and in the proximal humeri, proximal tibiae, and femora (Fig.9).
Fig,1. Neonatal lateral radiograph of left femur. The bones are dense with no linear striations
Fig.6. Lateralradiographoftheskullatl9 years age.Thereismarked sclerosis and thickening of calvarium, facial areas, and skull base
Fig. 2. Frontal radiograph of the chest of 1 month age. The proximal humeri have developed minimal dense striations. The clavicles are broad medially and laterally
Fig.'/. Frontal radiograph of distal femurs and proximal tibias at 20 years age. There are residual dense linear striations in diaphyseal and metaphyseal regions extending into epiphyseal areas. The growth plates have closed
Fig.3. Lateral skull at 8 years age. There is moderate sclerosis of skull base, mastoid area, and calvarium Fig.4. Frontal radiographs of the knees of patient at 8 years age. There are vertical linear densities in metaphyses of proximal tibias and distal femurs bilaterally Fig.5. Frontal radiograph of pelvis at 8 years age, Dense striations are present in femoral neck and iliac bones bilaterally
Fig,8. SPECT imaging of skull in axial projection. There are areas with increased tracer uptake (white areas) in frontal, occipital, skull base, and facial areas Fig.9. Radionuclide bone scan. There is increased tracer uptake in metaphyseal regions of distal femurs and proximal tibias in areas of linear striation seen on radiographs (Figs. 4 and 7)
59 Table 2. Clinicalfeatures of osteopathia striata with cranial sclerosis Large head with frontal and parietal bossing Hypertelorism with flat nasal bridge Hypoplasticmaxilla Palate anomalies (high arch, cleft) Marked hearing deficitwith chronic otitis media Stenotic external auditory canals Small, poorly aerated paranasal sinuses Nasal obstruction Cataracts Dental anomalies Facial palsy Eye muscleimbalance Mental retardation Headaches
OS-CS appears to be a specific bone dysplasia [12-15]. Kornreich  collected 20 patients with OS-CS from the literature, and we found, in addition, 13 other cases reported [15-25, 39, 40]. Another patient was mentioned but incompletely reported by DeKeyser et al. . The total number, including our case and the second of DeKeyser, is 35. OS-CS has shown an autosomal dominant mode of inheritance [12, 13, 25-27, 33] but has been sporadic . Sporadic cases probably represent a new dominant mutation so that OS-CS appears to be an autosomal dominant disorder. The age at the time of first diagnosis has varied from the newborn period to the 5th decade [14, 26]. OS-CS is 2.5 times more common in females who have more severe complications than do male patients [13, 15]. The clinical features of OS-CS are listed in Table 2. Our patient exhibited most of the clinical findings reported in other patients with OS-CS. The chronic middle ear problems with recurrent otitis media, severe hearing deficit, and pain have been very troublesome. Surgical intervention with attempted ossicular chain reconstruction and prosthesis was not successful. She has benefited very little from hearing aids. Hearing deficits have been present in half of the patients reported in the literature. Mental retardation has been present in many patients with OS-CS [13, 16, 21, 28, 32], but our patient has normal mentality and attends college. Cranial nerve deficiencies due to encroachment upon essential foramina of the skull by the sclerosing bone process have been noted in several patients. Facial palsy [14, 17, 31], a narrow optic foramen , and abducens nerve paralysis  have been reported. Our patient had eye muscle imbalance and deficient taste sensation on left side of tongue (3rd and 12th nerve deficiencies). Cataracts  and dental anomalies [18, 27] have been reported. Headaches have been present in two patients [12, 18]. The radiologic changes in patients with OS-CS are seen in multiple bones of the skeleton [13, 17]. The linear, striated densities seen in the long bones are present primarily in the metaphyses and adjacent diaphyses (Fig.2, 4, 7). The striated densities, which are parallel to the long axis of the bone, vary from minimal to marked  with the ti-
bias, femurs, humeri, and radius usually having the greatest involvement. The changes in the long bones may increase with age though in most patients they are non-progressive [12, 15]. The long bone striations may be present in the newborn  but could not be seen in our patient until after one month of age (Fig. 2). The vertebral bodies may show areas of patchy increased density [15, 21,29, 33], a minimal fine vertical striated pattern , or rather marked sclerosis [17, 21, 34], but in many patients, as ours, the spine has been normal. The pelvic bones (Fig. 5) may show linear striated opacities [13, 26]. In the thorax the ribs may show increased density and have linear dense striations parallel to the long axis , have cortical thickening [21, 34], and may be widened [3, 15, 26, 32]. The clavicles have similar dense changes and may show broadening of the medial ends as in our patient. The skull exhibits increased density in the basal portions and mastoid areas; the diploic space of the cranial vault is thickened and sclerotic (Figs.3, 6) and may increase progressively with age , as in our patient, or may remain unchanged . Frontal and parietal bossing is usually present. The sinuses are poorly developed and the facial bones more dense than normal. The mandible may be sclerotic [15, 16, 18] or have dense linear striations in the body or ascending rami [21, 25, 31]. An obtuse mandibular angle is sometimes present . Anomalies of the teeth have been present [19, 27]. The cranial nerve deficiencies are probably due to narrowing of the cranial nerve foramina by the sclerosing reactive process in the skull . Radionuclide bone scans in some patients with isolated OS have shown no increased uptake of the tracer in the bones of the extremities, spine, or pelvis [5, 35]. Increased uptake of 99mTc-MDP in the skull has been reported in 2 patients with OS-CS [17, 24] and in our patient (Fig. 8) suggesting an active metabolic process in the bone. The increased excretion of pyridinoline in our patient noted previously is also consistent with increased bone turnover (Table 1). The case reported by Rucker and Alfidi  which has been included in other reviews [15, 26] has been excluded. The bone changes were much coarser and more diffuse with minimal skull change. The marked cortical hyperostoses present were not seen in other reports of OS-CS. The authors agree with Paling  that this patient has another abnormality similar to the case reported by Fairbank  which was called "Hyperostosis generalisata with striations of bones." Computed tomography (CT) of the skull has been performed in at least 3 instances [16, 17, 25] and in our patient. The CT changes have been nonspecific. The basilar bones were dense with decreased pneumatization of the mastoid cells and normal ossicles in the middle ear . The cranium was large due to marked thickening of the calvarium . In one infant at 7 months age, CT examination of the head demonstrated large ventricles and large subarachnoid spaces consistent with cerebral atrophy without cranial sclerosis associated at the time but sclerosis eventually developed by 44/12 years . CT in our patient showed thickening of the calvarium and skull base and slight ventrieular dilatation of 3 years of age.
Conclusions A p a t i e n t , f o l l o w e d clinically f r o m b i r t h to 20 y e a r s of age, with o s t e o p a t h i a striata h a d p r o g r e s s i v e d e v e l o p m e n t of cranial sclerosis. This c o n d i t i o n r e p r e s e n t s a specific b o n e dysplasia with autosomal dominant inheritance. T h e i n c r e a s e d e x c r e t i o n of p y r i d i n o l i n e , as seen in o u r p a t i e n t , w i t h the use of scintigraphy, m a y b e useful in future p a t i e n t s to follow t h e m e t a b o l i c activity in b o n e .
Acknowledgements. The authors wish to thank and acknowledge the help of Jack E. Peterson, PhD, for his assistance in assembling the bibliography for the review of the literature.
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Note added in proof. Since preparation of this manuscript, an additional patient similar to the authors' patient has been reported with an excellent CT examination of the anomalies of the middle ear and temporal bones: Ordezin GT, Krasikov N (1993) CT of the temporal bone in a patient with osteopathia striata and cranial sclerosis. AJNR 14: 72.