46 Frontometaphyseal Dysplasia
FMD
Peculiar facial appearance, frontal torus, dental anom- alies, multiple joint contractures, skeletal dysplasia with hyperostosis, abnormal pelvis
Frequency: Rare (fewer than 50 published cases).
Genetics
X-linked dominant (OMIM 305620) with severe manifestations in males and variable manifestations in females; caused by gain of function mutations in the FLNA gene (OMIM 300017)
Clinical Features
• Frontal hyperostosis, prominent supraorbital ridges, broad nasal bridge, bushy eyebrows, low anterior hairline, hypertelorism, low-set and prominent ears
• High-arched palate, abnormal teeth (malaligned, small, missing)
• Small, pointed chin, micrognathia
• Relatively short trunk, pectus excavatum/carina- tum, winging of scapulae
• Severe thoracolumbar scoliosis, hyperlordosis
• Long extremities, asthenic habitus
• Arachnodactyly, ulnar deviation of hands
• Multiple joint contractures
• Poorly developed musculature, wasting of hand muscles
• Cardiac and esophageal defects, obstructive uro- pathy, upper airway malformations
• Hearing loss (conductive)
• Visual disturbances (optic nerve atrophy) Differential Diagnosis
• Pyle disease
• Craniometaphyseal dysplasia
• Infantile osteopetrosis
• Oto-palato-digital syndrome type I
• Melnick-Needles syndrome
Radiographic Features Skull
• Increased bone density, most prominent in supra- orbital area (torus-like sclerotic projections from supraorbital ridges of frontal bones), mild to mod- erate sclerosis of skull base
• Absence of frontal sinus pneumatization
• Maxillary hypoplasia, underdeveloped paranasal sinuses
• Severe hypoplasia of angle and condyles of man- dible
• Delayed closure of fontanels
• Defective dentition
• Large foramen magnum
• Ossicular chain abnormalities Pelvis
• Marked outward flaring of iliac wings
• Coxa valga
• Short and broad femoral neck, small femoral head Limbs
• Increased density of diaphyses of long bones
• Metaphyseal flaring of long tubular bones Hands and Feet
• Arachnodactyly (elongated and widened meta- carpals and phalanges), camptodactyly
• Defective modeling of the tubular bones of hands
• Osteopenia in the tubular bones of hands
• Carpal irregularities (fusions, resorption in older patients), increased carpal angle
Chest
• Irregular rib contour, flaring of ribs
• Abnormally high scapulae Spine
• Progressive scoliosis
• Flattening of lumbar vertebrae
• Increased interpediculate distance at lumbar level
• Anteriorly displaced odontoid
• Absent posterior arch of the atlas
• Cervical vertebral fusions (2nd and 3rd)
Frontometaphyseal Dysplasia 716
Frontometaphyseal Dysplasia 717
F
Fig. 46.1. a Three affected family members: patient 1, age 17 years (left), patient 2, age 16 years (right), and their mother, patient 3, age 34 years (middle). Note peculiar facies, with marked supraorbital ridges, broad nose, bushy eyebrows, small pointed chin, and low-set prominent ears. (Reprinted, with
permission, from Morava et al. 2003.) b Patient 4, age 17 years.
Observe prominent supraorbital ridges, bushy eyebrows, wide nasal bridge, and small chin. (Reprinted, with permission, from Canepa et al. 1996)
a b
Fig. 46.2. aPatient 1, age 17 years; b patient 2, age 16 years;
cpatient 3, age 34 years; d patient 4, age 17 years. Note dense torus-like projections from the supraorbital ridges of the
frontal bones, variable degrees of increased bone density in the cranial vault and skull base, and abnormal dentition.
(Reprinted, with permission, from Morava et al. 2003)
a b
c d
Bibliography
Fitzsimmons JS, Fitzsimmons EM, Barrow M, Gilbert GB.
Fronto-metaphyseal dysplasia: further delineation of the clinical syndrome. Clin Genet 1982; 22: 195–205
Franceschini P, Guala A, Licata D, Franceschini D, Signorile F, di Cara G. Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto-metaphyseal dysplasia. Am J Med Genet 1997; 73: 10–4
Glass RB, Rosenbaum KN. Frontometaphyseal dysplasia:
neonatal radiographic diagnosis. Am J Med Genet 1995; 57:
1–5
Gorlin RJ, Winter RB. Frontometaphyseal dysplasia – evidence for X-linked inheritance. Am J Med Genet 1980; 5: 81–4 Holt JF, Thompson GR, Arenberg IK. Frontometaphyseal dys-
plasia. Radiol Clin North Am 1972; 10: 225–43
Morava E, Illes T, Weisenbach J, Karteszi J, Kosztolanyi G. Clin- ical and genetic heterogeneity in frontometaphyseal dys- plasia: severe progressive scoliosis in two families. Am J Med Genet 2003; 116: 272-7
Nishimura G, Takano H, Aihara T, Ohashi H, Fukushima Y, Satoh M. Radiological changes of frontometaphyseal dys- plasia in the neonate. Pediatr Radiol 1995; 25 Suppl 1:
S143–6 Frontometaphyseal Dysplasia
718
Fig. 46.3. Patient 4, age 17 years. Note severe thoracolumbar scoliosis. (Reprinted, with permission, from Morava et al.
2003)
Fig. 46.4 a, b. Patient 3, age 34 years. Note fixed flexion con- tracture (camptodactyly) at proximal interphalangeal joint of 5th finger, and slender appearance of the tubular bones, with
mild cortical thickening in the diaphyses and osteopenia in the remaining portions. (Reprinted, with permission, from Morava et al. 2003)
a b
