A patient with Keipert syndrome and isolated fibrous dysplasia of the sphenoid sinus^†

To the Editor:

Keipert syndrome (KS), or nasodigitoacoustic syndrome (OMIM 255980), first described by Keipert et al. [1973] in two brothers, is characterized by unusual facial appearance, congenital sensorineural hearing loss, and skeletal anomalies including short terminal phalanges of the fingers and toes (brachytelephalangy), and broad thumbs and halluces with large, rounded epiphyses. Facial characteristics are hypertelorism, high and broad nasal bridge, depressed nasal ridge, underdeveloped maxilla, and exaggerated cupid bow upper lip vermillion [Keipert et al., 1973]. In 1996, Balci and Dagli described two male sibs with KS who had in addition pulmonary valve stenosis and hoarse voice. Since then, seven patients with this phenotype have been described (Table I) [Cappon and Khalifa, 2000; Reardon and Hall, 2003; Dumic et al., 2006; Amor et al., 2007; Nik-Zainal et al., 2008].

The mode of inheritance for KS is thought to be X-linked recessive possibly mapped at Xq22.2–Xq28 [Amor et al., 2007]. However, Dumic et al. [2006] documented a female patient whose father was also mildly affected and, thus, they proposed autosomal dominant inheritance. But, the phenotype in these patients was not completely classical (Table I).

We had the opportunity to investigate a young male patient who had the classical findings of KS as well as isolated fibrous dysplasia (FD) of the sphenoid sinus. This 14-year-old boy had undergone surgery for peripheral pulmonary artery stenosis and was referred for evaluation of his unusual face, hearing loss, and headaches. He was the third child of healthy, non-consanguineous parents, and his two brothers were healthy and had no similar abnormalities. The patient's mother had been 35 years at the time of his birth. Pregnancy was uncomplicated. The patient's birth weight was 2,500 g (3rd centile). He had reached all motor–mental development milestones at a normal age.

At our examination, his height was 155.3 cm (10th to 25th centile), weight was 42.1 kg (10th to 25th centile), and skull circumference was 52.5 cm (25th to 50th centile). The patient had hypertelorism, underdeveloped maxilla, a high nasal bridge, depressed nasal ridge, short columella, exaggerated cupid bow upper lip vermillion, retrognathia, and low-set and posteriorly rotated ears (Fig. 1A,B). His palate was high and narrow, his fingers and toes were short, and his thumbs and halluces were broad. His second toes were longer than the other toes (Fig. 2A,B). Radiographs showed short terminal phalanges of fingers and toes, and broad thumbs and halluces with large epiphyses, especially of the halluces (Fig. 3A,B). Skull X-rays showed bilateral underdeveloped maxillae, nasal septal deviation, and hypertrophic conchae. Renal ultrasonography and radiographs of the spine and long bones gave normal results. Skull computed tomography (CT) was done to investigate his headaches and demonstrated an expansive sclerotic lesion filling the sphenoid bone, with heterogeneous ossifications that displayed the “ground-glass” appearance characteristic for FD (Fig. 4).

A complete blood count and routine biochemical tests of hepatic and renal function did not show abnormalities. Hearing tests revealed mild conductive hearing loss of 28 dB bilaterally. Classical cytogenetic analysis and fluorescent in situ hybridization analyses for del22q11.2 showed a normal male karyogram (46,XY).

The patient had all characteristics of KS, though his hearing loss was conductive as opposed to sensorineural. The main findings for this patient are compared to those of the 11 earlier described patients in Table I.

FD is an uncommon locally destructive but otherwise benign bone disorder of unknown etiology, in which normal medullary bone is replaced by fibrotic and osseous tissue. It shows a predilection for cranial and facial bones and most frequently affects the mandible and maxilla. Solitary involvement of the sphenoid sinus, as observed in our KS patient, is rare [Buyuklu et al., 2005]. There are three subtypes of FD: type 1 or monostotic type (single bone involvement). It is the most frequent and the mildest type (70% of all patient); type 2 or polyostotic type; and type 3 or McCune–Albright syndrome, which is the most severe form. When the sphenoid sinus is involved, the most common symptoms are headache, diplopia, visual problems, nasal stuffiness, and ptosis [Buyuklu et al., 2005]. In the present patient, FD subtype 1 can be diagnosed presenting with nasal stuffiness and headaches.

FD accompanying KS has not been documented previously, and isolated occurrence of FD in the sphenoid sinus is rare. The co-occurrence is either coincidental or FD may be infrequently a manifestation of KS. It requires reports on additional cases to determine this.