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Craniodiaphysial dysplasia is an extremely rare genetic disorder characterized by a severe form of bone dysplasia and a distinctive facial dysmorphisms, as a result of a massive generalized hyperostosis and sclerosis, primarily involving the facial bones and the skull. We present a 10-years-old girl referred to an otolaryngology consultation with complaints of progressive hearing loss. The clinical aspects, pathogenesis and management of this disease are also review in this paper. Furthermore, we describe the first case of craniodiaphysial dysplasia rehabilitated with Bone-Anchored Hearing Aid, despite the concerns inherent to the involvement of the skull bone that characterizes the disease.

The skeletal remains of a male aged 45–55 years displaying several bone anomalies were unearthed from the Alghero (Sardinia) plague cemetery ‘lo Quarter’, a burial site dating back to the 1582–1583 AD outbreak. The skeleton, whose stature is about 165 cm, presents a bilateral hyperostosis with increased diameter of the diaphyses of all the long bones of the upper and lower limbs; the metaphyses appear to be involved, while the epiphyses are spared. Marked thickening of the cranial vault is also evident. Radiological study showed irregular cortical thickening and massive endoperiosteal bone apposition; sclerotic changes are observed in the diaphysis of some metacarpals. Computed tomography (CT) cross sections of the long bones displayed a thickening of the cortical portion and endoperiosteal bone apposition. The individual was affected by a sclerosing bone dysplasia, a genetic disease characterized by increased bone density. In differential diagnosis, several sclerosing bone dysplasia, such as hyperostosis corticalis generalisata, craniodiaphyseal dysplasia, craniometadiaphyseal dysplasia, pachydermoperiostosis and Camurati–Engelmann disease, as well as other disorders characterized by sclerosing manifestations, such as Erdheim–Chester disease, mehloreostosis and skeletal fluorosis, need to be considered. The anomalies observed in skeleton 2179 fit with the features of Camurati–Engelmann disease, which is the most likely candidate for final diagnosis. It is highly challenging to evaluate how such a condition may have influenced the individual's lifestyle in terms of development, mobility and quality of life. This individual was probably symptomatic and must have experienced common clinical symptoms, such as pain in the limbs and fatigability. However, the strong development of the muscular insertions and the degenerative changes in the upper limbs suggest that the mobility problems should not have prevented him from reaching a mature age and from performing essential daily activities. The presented case is the unique paleopathological evidence of Camurati–Engelmann disease so far diagnosed. Copyright © 2015 John Wiley & Sons, Ltd.

WOS: 000392470000009, Objective Chiari malformation type-I (CM-1) is described radiographically as a simple displacement of the cerebellar tonsils at least 5 mm below the foramen magnum (FM). If CM-1 exists due to hyperostosis of the cranial bones, the authors were not able to determine a common consensus for the treatment of CM-1 and syringomyelia. Methods A 31-year-old-female presented to our hospital with bilateral facial paralysis, hypoesthesia and motor loss of the extremities. The patient had bilateral gag reflex loss, phonation disorder and dysarthric speaking. Sensory and motor deficits were available at the bilateral upper and lower extremities. The skeletal radiographs revealed extensive thickening and sclerosis of the calvarial and facial bones, moderate widening and sclerosis of the clavicles and ribs, and that the internal auditory canal (IAC) and the optic foramen (OF) were narrowed. CM-1 and syringomyelia secondary to the small posterior fossa were due to calvarial hyperostosis. The patient underwent posterior fossa decompression and duraplasty. In addition, a syringosubarachnoid shunt was placed at the level of C7-T1. The symptoms of lower cranial nerve palsy and motor loss were recovered, but the symptoms of the foraminal stenosis, such as visual and auditory losses and facial paralysis were not recovered in any way. Conclusion We described in this case report CM-1 as a late complication of craniodiaphyseal dysplasia (CDD), and the difficulties in its treatment. In the treatment of these patients with CDD, posterior fossa decompression and syringosubarachnoid shunting are necessary, in spite of all the risks of these procedures.

Craniodiaphyseal dysplasia is a severe disorder characterized by distinctive facial dysmorphisms, including prominent zygomatic bones, broadening of the center of the face, hypertelorism, a small upturned tip of the nose and massive hyperostosis and sclerosis of the skull and facial bones. The sclerosis is severe and is referred to as “leontiasis ossea” (leonine faces), and the bone deposition causes progressive stenosis of the craniofacial foramina (1-5). The skull and facial hyperostosis result in an increasing head circumference, paranasal bossing, nasal bridge distortion and an alteration in the orbital alignment. Radiographic features consist of osteosclerosis and hyperostosis of the skull and facial bones and, to a lesser degree, the diaphyses of the tubular bones. There is often secondary optic atrophy and deafness, and epilepsy and mental retardation have both been reported (6,7). Familial osteoectasia with macrocranium and hyperphosphatasia are features encountered in juvenile Paget's disease (juvenile deforming cortical hyperostosis) (7). Genotypical diseases of familial osteoectasia are characterized by Cushingoid facies, limb deformities (from generalized osteoporosis) and retarded growth (8,9).

We describe a mother and her male infant affected with a craniotubular dysplasia characterized by severe craniofacial hyperostosis and sclerosis with obliteration of paranasal sinuses and foramina of the skull base. Subsequent severe bilateral hearing loss and facial diplegia with relative sparing of the optic nerves were noted. The long bones show extreme asymmetric hyperostosis and sclerosis of the diaphyses and evidence of a modelling defect in the metaphyses. The spine, ribs, clavicles, and pelvis all show some degree of sclerosis and defective modelling, but are less severely involved. According to the definition by Gorlin, this disorder would best be classified as craniodiaphyseal dysplasia. Distinguishing features in these two patients as contrasted to previously described cases include a greater degree of hyperostosis and sclerosis than that described for other patients with craniodiaphyseal dysplasia, apparent dominant transmission, and significant metaphyseal involvement.

We describe a boy and his mother affected with craniodiaphyseal dysplasia (CDD). The boy had a very severe form of the disease with extensive osteosclerosis already at birth. Facial diplegia, bilateral hearing loss and optic nerve atrophy were early, severe complications of the disease. At age 7 years progressive genu valgum and unusual epimetaphyseal radiographic appearances suggested hyperparathyroidism. This was confirmed by biochemical tests. Because of some facial similarity between the asymptomatic mother and the propositus, a limited skeletal survey of the mother was performed. It demonstrated cranial osteosclerosis and hyperostosis. It is possible that the mother has somatic mosaicism for a mutation of the genes causing CDD. © 2007 Wiley-Liss, Inc.

We report the magnetic resonance (MR) imaging findings in a 4-year-old girl with characteristic radiographic and computed tomography (CT) features of craniodiaphyseal dysplasia. MR imaging exquisitely depicted cranial nerve compression, small foramen magnum, hydrocephalus, and other intracranial complications of this syndrome. A syrinx of the cervical spinal cord was demonstrated. We suggest that MR imaging become a routine component of the evaluation of these patients.

We describe a rare syndrome characterized by severe craniofacial hyperostosis, sclerosis, obliteration of paranasal sinuses and foramina of skull base, in a 10-year-old female child who presented with abnormal facial features and recurrent dacryocystitis due to narrowing of nasolacrimal duct.

We report on a 4-year-old boy with craniometadiaphyseal dysplasia (CMDD), wormian bone type. Component manifestations include a large head with prominent forehead, skull changes showing multiple wormian bones, wide long tubular bones without the usual metaphyseal flare, wide and short tubular bones without the normal diaphyseal constriction, and wide ribs and clavicles. In addition to these findings, the propositus, his brother, his father, and a paternal aunt all have parietal protuberances, which seem not related to CMDD. Parental consanguineity supports the autosomal recessive transmission of the condition.

Craniodiaphyseal dysplasia is a rare, sporadic form of craniotubular bone dysplasia, characterized by massive generalized hyperostosis and sclerosis, particularly of the skull and facial bones, leading to severe deformity. The clinical course is typically characterized by progressive encroachment of the craniofacial foramina and brain by the relentless deposition of bone. Compression of cranial nerves, the foramen magnum, and intracranial contents commonly leads to blindness, loss of hearing, and death. This report describes a unique case of craniodiaphyseal dysplasia manifesting with asymmetric craniofacial and axial hyperostosis. The tubular bones demonstrated the characteristic diaphyseal endostosis, undertubulation, and relative overgrowth on the involved side. Significant brain compression with signs and symptoms of increased intracranial pressure was managed successfully with decompressing craniectomy at age 12 years, enlarging the anterior and middle fossae. Calvarial thickness measured nearly 4 cm. Further calvarial, midfacial, and mandibular recontouring were performed 6 and 22 months later. Follow-up in our case indicates that close observation is mandatory to manage further progression of the disease.

Summary A nine-year-old boy with craniodiaphyseal dysplasia (CDD) presented for mandibular reduction. Patients with CDD present problems to the anaesthetist, specifically difficulties with airway management and tracheal intubation. This child was managed using laryngeal mask airway (LMA) guided fibreoptic intubation. Spontaneous respiration was maintained throughout intubation, following which ventilation was controlled and anaesthesia was provided using nitrous oxide, isoflurane and fentanyl. The perioperative management is described.

Craniometaphyseal and craniodiaphyseal dysplasia are rare genetic disorders of bone due to modelling errors of long bones and skull bones. These syndromes present with multiple ENT symptomatology from an early age. The diagnostic distinction can now be made radiologically by serial skeletal survey which is important for prognosis. We review the clinical, radiological, computed tomography (CT) scan, otological, audiological and histopathological findings in two cases with craniodiaphyseal, and two cases with craniometaphyseal dysplasia, and report our experiences of medical and surgical treatment to date.In the craniodiaphyseal dysplasia, the hearing abnormality progressed from an initial conductive to a mixed loss on serial audiometric follow up. Temporal bone CT scans showed narrowing of the middle ear cavity, internal auditory meatus, and facial nerve canal at the geniculate ganglion. Benefits from choanal stenosis surgery, craniofacial remodelling and dacrocystorhinostomy were shortlived. Calcitriol therapy with a low calcium diet did not alter the clinical course of progression in our cases. The underlying defect, causing net bone formation in these phenotypically similar syndromes, appears to be different when based on the differing biochemical responses to calcitriol and bone biopsy findings. Increased numbers of osteoblasts were found in bone biopsies from both cases with craniodiaphyseal dysplasia.Early recognition is crucial in these conditions as therapy directed at the underlying bony defect has the best chance of success if initiated in infancy (Cole et al., 1988; Fanconi et al., 1988; Key et al., 1988).

Chapter 113 covers craniodiaphyseal dysplasia (MIM 112860, 218300), including major clinical findings, radiographic features, and differential diagnoses.

Lenz-Majewski hyperostotic dwarfism is an extremely rare syndrome with moderate to severe mental retardation and no previously identified brain abnormalities. We describe the seventh case and note dysgenesis of the corpus callosum in this patient.

Hyperostotic bone dysplasias are characterized by progressive hyperostosis and sclerosis of the cranium and facial bones. As a result of progressive bony overgrowth, intracranial pressure may increase and lead to brain and nerve compression, cranial nerve palsies, and an increased incidence of seizures. The long bones often exhibit defective modeling as well as variable degrees of metaphyseal and diaphyseal hyperostosis. In addition, the axial skeleton (including the pelvis) is often hyperostotic and sclerotic. The clinical features of these disorders may have relevance to the outcome of pregnancy; however, there are no reports on the management and pregnancy outcome of patients affected with hyperostotic bone disease. In this report, we describe the course of two pregnancies in a woman with craniodiaphyseal dysplasia (a rare craniotubular dysplasia). Prenatal assessment, method of delivery, choice of anesthesia, and neonatal management are discussed. Although this disorder is rare, the pathophysiologic considerations relevant to pregnancy outcome may be applicable to the management of pregnant women with other hyperostotic bone dysplasias.

Sclerosing bone dysplasias are a poorly understood group of developmental anomalies, much of whose etiology is still obscure. The list of conditions constituting this group is relatively short: osteopetrosis (Albers-Schönberg disease), pycnodysostosis (Maroteaux-Lamy disease), enostosis (bone island), osteopoikilosis, osteopathia striata (Voorhoeve disease), progressive diaphyseal dysplasia (Camurati-Engelmann disease), hereditary multiple diaphyseal sclerosis (Ribbing disease), four types of endosteal hyperostosis (van Buchem disease, Worth disease, Nakamura disease, and Truswell-Hansen disease), dysosteosclerosis, metaphyseal dysplasia (Pyle's disease), craniometaphyseal dysplasia, melorheostosis (Leri disease), and craniodiaphyseal dysplasia. There are instances in which two or more of the above disorders coexist. These are termed "overlap syndromes", most commonly involving osteopathia striata, osteopoikilosis, and melorheostosis. A classification of these dysplasias is elaborated based on a targetsite approach that views them as disturbances in development associated with the processes of either endochondral or intramembranous bone formation, or both. Accumulated evidence suggests that many of these disorders stem from common defects in bone resorption and/or formation during the processes of skeletal maturation and modeling. Finally, the subgroup of overlap syndromes is emphasized as indicating a strong interrelationship between the sclerosing dysplasias of bone, with perhaps a common pathogenesis for many.

Background Most cases of generalized hyperostosis of the skull are associated with Camurati-Engelmann disease, craniodiaphyseal dysplasia, Worth-type endosteal hyperostosis, or sclerosteosis. Infrequently, a Chiari malformation may also be described. We present the case of a patient with acquired Chiari malformation secondary to hyperostotic skull formation whose findings did not fit into any of the 4 usual conditions. We review the literature on generalized hyperostosis of the skull and discuss the appropriate treatment based on our analysis of the literature and the patient's imaging results. Case Description A 26-year-old woman presented with headaches, vomiting, and visual loss. Imaging revealed hyperostosis of the skull and an acquired Chiari I malformation. Intracranial pressure was markedly increased. She underwent a reduction craniotomy with subtemporal decompression and had good clinical improvement. Conclusion Chiari malformation in association with hyperostosis of the skull is an unusual finding. Our patient could not be classified into any of the 4 main hyperostotic conditions. Careful attention to imaging identified the hyperostosis and deflected treatment from the standard for Chiari I malformation, suboccipital decompression, which could have proved fatal. Instead, a reduction craniotomy with subtemporal decompression relieved the source of the increased ICP and of the downward tonsilar displacement.

We report two pairs of siblings with the syndrome cranioectodermal dysplasia who have subsequently developed chronic renal failure secondary to tubulo-interstitial nephropathy. Renal disease has not been described before in this rare syndrome but has now occurred in four of the seven reported cases. Children with cranioectodermal dysplasia appear to be at significant risk of developing chronic renal failure. This is important information for clinicians looking after such children, and their families, when considering the long-term prognosis and management.

We report a 56-year-old woman, mainly suffering from painful legs and the inability to run. Radiologically, marked sclerosis and hyperostosis of the skull bones is present resulting in macrocephaly. Most tubular bones of the limbs, as well as the clavicles, are affected by sclerosis. By mutation analysis of the TGFB1, SOST and LRP5 genes, we were able to exclude the diagnoses of Camurati-Engelmann disease, Van Buchem disease, sclerosteosis, high-bone-mass trait and endosteal hyperostosis (Worth type). We believe this patient represents one of the very few examples of adult craniodiaphyseal dysplasia with a mild form of the disease and moderate facial changes.

The procedure of dacryocystectomy is described in a child with craniodiaphyseal dysplasia. Fibrin tissue adhesive is used to distend and delineate the lacrimal sac and fistula to aid complete dissection.

Craniometaphyseal dysplasia is a rare genetic bone disorder characterized by undertubulation of the long bones, especially in the lower extremities, and sclerosis of the skull base. Differentiation from other sclerosing bone dysplasias, including metaphyseal dysplasia (Pyle's disease), craniodiaphyseal dysplasia, and diaphyseal dysplasia is based largely on characteristic radiographic findings. Radionuclide bone scans usually are not necessary for diagnosis, but are helpful in demonstrating the abnormal bone metabolism. The authors report the first whole-body bone images in a patient with craniometaphyseal dysplasia, demonstrating the abnormal bone activity over time.

The heterogeneous group of craniotubular dysplasias is characterized by modeling errors of the craniofacial and tubular bones. Some conditions in this category cause not only skeletal abnormalities but also a variety of mesoectodermal dysplasias, as exemplified in Lenz-Majewski syndrome (MIM 151050), which comprises craniodiaphyseal dysplasia, failure to thrive, mental retardation, proximal symphalangism, enamel hypoplasia, and loose skin. We report on a boy with a hitherto unknown multisystem disorder, including skeletal changes that were regarded as a form of craniotubular dysplasia. The patient had a large head, exophthalmos, a broad nasal root, anteverted nostrils, large auricles, thick lips, micrognathia, severe postnatal growth retardation with emaciation, severe mental retardation, sparse hair growth, enamel hypoplasia, and thin, loose skin with hyperlaxity. Skeletal changes consisted of thickened calvaria, sclerosis of the skull base and facial bones, thick ribs, and metaphyseal undermodeling of the tubular bones. In addition, generalized osteopenia was evident. The present disorder overlaps phenotypically with Lenz-Majewski syndrome; nevertheless, the absence of diaphyseal hyperostosis and proximal symphalangism in the present patient was not consistent with Lenz-Majewski syndrome.

To our knowledge, this is the first description of the histopathology of the temporal bone from a case of craniodiaphyseal dysplasia. The air spaces of the mastoid, external auditory canal, and middle ear cavity are reduced by hyperostotic bone. The ossicles are also deformed by the bony overgrowth. Anomalous ossicles with hyperostosis could affect the air conduction. Even though the internal auditory canal is somewhat elongated and narrow, no labyrinthine abnormalities can be attributed to the abnormal bone. Facial nerves run through abnormal courses but the geniculate ganglion cells are not involved. The VIIIth nerve dysfunction in this case could be due to mechanical damage of the nerve fibers and/or impaired vascular supply by the hyperostosis.

The autosomal recessive form of craniometaphyseal dysplasia was ascertained in two sibships with two affected individuals each. All four parents were normal and in one case they were consanguineous; both families were living in Caracas but had their origins in Tenerife Island (Canary Islands), although no genealogic link between them could be established. The age of the patients ranged from 6 to 14 years and the main clinical alterations were a thick bony wedge over the bridge of the nose, dystopia canthorum, ocular hypertelorism, enlarged malar prominences and mandible, wide alveolar ridges, dental abnormalities, and genu valgum; narrowing of the nasal passages led to mouth breathing. A slight, mixed hypoacusia was present in two patients; no other signs of cranial nerve involvement were detected. The cardinal radiographic features were hyperostosis and sclerosis of the calvarium, the base of the skull, and the facial bones and mandible; increased bone deposition on the walls of the paranasal sinuses; under-pneumatization of mastoid cells; cortical hyperostosis of the diaphyses of the short and long tubular bones, and gradual, club-shaped widening of the metaphyses, which had thin cortex and undermineralized medullary bone. The clinical and radiologic alterations had an increasing gradient of severity with age. The phenotype of recessive craniometaphyseal dysplasia is not clearly differentiated from the dominant form but easily so from two other recessive conditions with which it was formerly confused: Pyle disease and craniodiaphyseal dysplasia.

For some reasons skull findings in Jansen's Metaphyseal Dysplasia have been largely neglected. A survey of the seven known cases (three of them being primarily observed and described by two of the authors) disclose important and constant alterations, namely pronounced basilar thickening and sclerosis, prominent supraorbital and zygomatic arches, underdevelopment of the paranasal sinuses with sclerosis of the adjacent bone, and hypoplasia of the mandible. These alterations give rise to distinct and fairly specific features. The relationship to other craniotubular disorders, such as craniodiaphyseal dysplasia, craniometaphyseal dysplasia, and frontometaphyseal dysplasia is discussed.

A small number of cases have been described of Craniodiaphyseal Dysplasia including early “leontiasis ossea” with progressive bony encroachment of skull foramina leading to severe neurological impairment in the first decade. Total thyroidectomy to remove a suspected source of excessive calcitonin was carried out in the only previous case where therapy was attempted. We report the case of the daughter of a Chief Petty Officer who presented with choanal stenosis at birth and who died at age 7 years with massive hyperostosis and sclerosis especially involving the skull and facial bones. Partial responsiveness of this condition to therapy with synthetic human calcitonin was suggested by a fall in the velocity of increase in her head circumference and changes in serum total and bone isoenzyme alkaline phosphatase. Management of the metabolic, neurological and social aspects of this condition is discussed.

A Negro girl has been followed from age 1 1/2 to 6 years for a severe musculoskeletal disorder with many of the clinical and roentgenological characteristics of Camurati-Engelmann disease. Atypical features, however, have included a geographic pattern of sclerosis of the long bones, a markedly increased density of the neural arches of the vertebral column, and a sharply demarcated sclerosis in the calvaria. The findings in the long bones and spine have become somewhat less pronounced over a five-year period, but the sclerosis of the skull has increased in both extent and thickness. Initially thought to have Camurati-Engelmann disease, the patient now is considered, on the basis of skeletal changes during this time, to have a diagnosis of craniodiaphyseal dysplasia.

✓ In a patient with Camurati-Engelmann disease, orbital and optic nerve decompression resulted in improvement of papilledema. Subsequent x-ray films of the optic canals, however, revealed reconstitution of osseous optic canals bilaterally, and papilledema has returned in one eye. Definitive treatment of this dysplastic metabolic bone disorder rests in the control of rapid abnormal bone formation.

The results of histologic, microradiographic and electron microscopic investigations carried out on two bone biopsies pertaining to a case of craniodiaphyseal dysplasia are reported. They show that the affected skeletal segments are chiefly characterized by enhancement of bone volume, and defective calcification of the bone matrix. Moreover, interstitial calcification of skeletal muscle has been found.

THIS REPORT was prompted by the discovery of a patient with an unknown osseous dysplasia. We have chosen the namefrontometaphyseal dysplasiato designate this new syndrome of multiple bony defects which is apparently distinct from Pyle's disease, craniometaphyseal dysplasia, craniodiaphyseal dysplasia, and osteopetrosis. Report of a Case A 19-year-old white male patient was admitted for cardiac evaluation (Fig 1). On admission, he was noted to have multiple skeletal anomalies. The patient's father, mother, sister, and two brothers were normal. Consanguinity was denied. The patient was known to have a heart murmur since birth. Five years before admission, increased fatigability and exertional dyspnea were noted. Past history indicated that the patient had a 50% to 60% hearing loss bilaterally. Physical examination revealed a well-nourished boy with a marked supraorbital ridge, slight facial asymmetry, wide nasal bridge, mild antimongoloid obliquity, hirsutism above the eyebrows, and a small pointed chin (Fig 2).