Frontometaphyseal dysplasia

Alberto Sosa Olavarria, A, MD, PhD, Diaz Guerrero, L, MD, Garcia M, MD, Pereira D, MD, Martines M, MD

Perinatology Unit, Carabobo University, Valencia - Venezuela.


In spite of the large quantity of skeletal dysplasias that have been diagnosed prenatally by ultrasound there is no report of the syndrome that was first described by Gorlin and Cohen in 1969[1]. The syndrome consists in a rare craniotubular dysplasia with progressive join ankylosis and a particular face. It is an X-linked dominant trait or an autosomal dominant defect. In this case we related the clinical features of the first case of antenatal diagnosis of a frontometaphyseal dysplasia in a male fetus. The typical phenotype of the mother and her X-rays examination allowed the fetal diagnosis.

Case Presentation

A 34-year-old pregnant patient, with a previous history of a neonatal death for respiratory failure origin, was referred to the Perinatology Unit of the Carabobo University (UPUC) at 29 weeks+3days pregnancy. The physical exam of the mother patient showed a characteristic phenotype: square face, wide forehead with posterior inclination, prominent supraciliary ridges and zygomatic arches, sharp nose tip, depressed nasal bridge and prominent upper lip. The sonographic study revealed a fetal biometry of 29 weeks+3days, fetal growth at the 50th percentile with the following findings: flat profile, depressed nasal bridge, macrognathia, reduced thorax, hands clinodactyly, sandal gap, short fifth finger of the hand. The left kidney had a cystic appearance. Amniotic fluid and placenta were normal.

This section of the face (vertex to the right) demonstrates the eye and the supraorbital ridge


These are the two feet, not hands:



A cross section through the tibial metaphysis


This is a hand next to the face


A narrow chest:


The newborn


And the mom (the eyes are masked for privacy reasons).


The baby and the mom"s legs



The child"s chest film 




and feet.


We proposed the following diagnostics: oculo-digito-plantar syndrome,  trisomy 10, oral-facial-digital syndrome (Moorsh).

Radiological studies of the mother were performed.

We repeated the sonographic study 9 weeks later with the following findings: 38 weeks gestation, the fetus looks very similar to his mother, prominent supraciliary ridges, flat nose with depressed bridge, prominent inferior lip, altered thorax/abdomen relation with altered ribs, curved long bones of the inferior extremities, tibial metaphyses 22mm, clinodactyly of the hands, toes in radial disposition, long phalanx in hands with the exception of the little finger. Hypoplastic left kidney. Male gender. Cryptorchidism.

The radiological study of the mother reported de diagnosis of Gorlin-Cohen frontometaphyseal dysplasia and thus this differential diagnosis was given to the fetus in view of the similar phenotype that was recognized in the sonographic study. The newborn was delivered by cesarean section. The birthweight was 3.300g with the characteristic findings named before. The mother's family recognized the baby's appearance as identical to that of the one that died before. The mother and newborn were discharged in good condition. Genetic study of the newborn demonstrated a normal male karyotype. At 3 month of age the boy presented with ventriculomegaly and left kidney atrophy, he was sent to neurology, nephrology and orthopedic for assistance and follow-up


Definition: Frontometaphyseal dysplasia is an uncommon genetic syndrome affecting bone and connective tissue.

Clinical manifestations: The disorder is characterized by the following:

  1. Typical face with rough trait, prominence of supraorbital ridges, prominent zygomatic arches antimongolian inclinations of the eyes, sharp end and wide root nose, depressed nasal bridge, triangular mouth with prominent upper lip, antegonial notching of the mandible, broad forehead, square face and elevated palatine vault.
  2. The limbs have partial ankylosis, rough hands, arachnodactyly with elongated proximal and middle phalanges, clinodactyly of hands and feet, wide interdigital feet space with radial disposition of the toes, second toe larger than fist one.
  3. Reduced thorax with asymmetry, pectus excavatum.
  4. Other findings include cryptorchidism and congenital urinary tract malformations. Radiology shows broad long bones metaphyses, elbow, wrist and knee ankylosis, wide posterior foramen magnum and increased interpedicular distance of the lumbar spine, narrow and twisted ribs with posterior segment deformities, wide and flare iliac bones. Long bones have flared metaphyses and bowed body

The manifestations are more severe in males. Normal intelligence and neurologic evolution have been described although the individuals can be severely affected

The differential diagnosis is with Pyle syndrome, craniometaphyseal dysplasia, Melnick-Needles syndrome, Shprintzen - Goldberg syndrome and diaphysary dysplasia (or Kenny-Caffey"s syndrome).

The prognosis in the anomaly depends on the progression of the ankylosis, the thoracic restriction that can lead to a severe acute ventilatory insufficiency or to a progressive respiratory failure (right-side failure). Other complications such as genitourinary tract obstructive anomalies and progressive hydrocephaly have also been reported.

Inheritance: X-linked dominant trait or autosomal dominant[3],8,[4],[5].

Previous cases: Gorlin and Cohen1 described a patient with extraordinarily marked frontal hyperostosis giving great prominence to the supraciliary ridges, underdeveloped mandible, cryptorchidism, subluxation of the radial heads and metaphyseal dysplasia resembling that in Pyle disease. Danks et al[6] have studied an isolated case with progressive contracture of the fingers and lysis and fusion of carpal bones. Nothing was known of the genetic of this disorder until Weiss at al[7] observed it in a black male whose mother had the same disorder, and Gorlin and Winter observed a family suggesting X-linked inheritance and raised the question of whether this might be the case in the family of Weiss inasmuch as the mother was more mildly affected than the son. Gorlin and Winter found evidence for X-linked inheritance with severe manifestation in males and variable manifestations in females.

Fitzsimmons et al[9] reported 4 cases in 1 family: grandmother, mother, son and daughter. The male had obstructive uropathy at birth. The authors found reports of associated renal abnormalities in 3 other males. The male also had severe congenital stridor from subglottic stenosis and tracheal web. On the basis of experience with 2 newborn sons of an affected mother, Glass and Rosenbaum[10] commented on the difficulties in diagnosing frontometaphyseal dysplasia in the neonatal period. In both newborns, bone density was generally increased, but most markedly in the skull base. The coronal skull sutures were partially fused, the metaphyses of all the long bones were flatten. As in the mother, the ribs were unusually shaped and there was an anterior bony spur from the mandible, both children died neonatally of severe congenital heart disease.

Complications: Complications can be orthopedic[11], neurological, urinary[12], cardio-respiratory insufficiency[13],[14], laryngo-tracheal stenosis[15]

Prognosis: Our observations confirm the previous report of severe manifestations in males with gloomy prognosis and variable manifestations in females.

Management: Cranioplasty may be of help in correcting the fronto-orbital deformity in frontometaphyseal dysplasia[16]


[1] Gorlin, R.; Cohen, M. Frontometaphyseal dysplasia: a new syndrome. Am J Dis Child 118: 487-494, 1969.

[2] Nishimura G, Takano H, Aihara T, Ohashi H, Fukushima Y, Satoh M Radiological changes of frontometaphyseal dysplasia in the neonate. Pediatr Radiol 1995 Nov;25 Suppl 1:S143-6

[3] Beighton P, Hamersma H Frontometaphyseal dysplasia: autosomal dominant or X-linked? J Med Genet 1980 Feb;17(1):53-6

[4] Kassner EG, Haller JO, Reddy VH, Mitarotundo A, Katz I Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance. Am J Roentgenol 1976 Dec;127(6):927-33

[5] Weiss L, Reynolds WA, Szymanowski RT Frontometaphyseal Dysplasia. Evidence for dominant inheritance. Am J Dis Child 1976 Mar;130(3):259-61

[6] Danks, D.; Mayne , V.; Hall, R.; McKinnon, M. Frontometaphyseal dysplasia: a progressive disease of bone and connective tissue. Am J Dis Chil 123: 254-258, 1972

[7] Weiss, L.; Reynolds, W. ; Szymanowski, R. Frontometaphyseal dysplasia:  evidence for dominant inheritance Am J Dis Child. 130: 259-264, 1976.

[8] Gorlin, R.; Winter, R. Frontometaphyseal dysplasia – evidence for X-linked inheritance. Am J Med Genet. 5:81-84, 1980

[9] Fitzsimmons, J.; Fitzsimmons, E.; Barrow, M.; Gilbert, G. Fronto-metaphyseal dysplasia: further delineation of the clinical syndrome. Clin Genet 22: 195-205, 1982.

[10] Glass, R.; Rosenbaum, K. Frontometaphyseal dysplasia: neonatal radiographic diagnosis. Am J Med Genet 57: 1-5, 1995.

[11] Medlar RC, Crawford AH Frontometaphyseal dysplasia presenting as scoliosis. J Bone Joint Surg Am 1978 Apr;60(3):392-4

[12] Kanemura T, Orii T, Ohtani M Frontometaphyseal dysplasia with congenital urinary tract malformations. Clin Genet 1979 Dec;16(6):399-404

[13] Lipson E, Ahmed T, Kiel MH, Chediak AD Restrictive chest bellows disease and frontometaphyseal dysplasia. Chest 1993 Apr;103(4):1264-5

[14] Swank SM, Winter RB, Moe JH Scoliosis and cor pulmonale.Spine 1982 Jul-Aug;7(4):343-54

[15] Leggett JM Laryngo-tracheal stenosis in frontometaphyseal dysplasia. J Laryngol Otol 1988 Jan;102(1):74-8

[16] Kung DS, Sloan GM Cranioplasty in frontometaphyseal dysplasia. Plast Reconstr Surg 1998 Sep;102(4):1144-6

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