Frontometaphyseal dysplasia is a rare genetic syndrome characterized by skeletal dysplasia comprising hyperostosis of the skull and modeling anomalies of tubular bones [1
]. The most common manifestations include supraorbital hyperostosis, hypertelorism, down-slanting palpebral fissures, and generalized skeletal dysplasia. The dysplasia manifests with thickening of the calvarium; agenesis of the frontal, ethmoidal, and sphenoidal sinuses; and bowing and undermodeling of tubular bone diaphyses and metaphyses [3
A proportion of individuals have missense mutations or small deletions in an X-linked gene, FLNA
. The possibility of X-linked inheritance was suggested because affected individuals show some variation in clinical severity of the disease, and manifestations in females are normally milder than in males [5
]. Despite this finding, the observation that there is partial expression in female carriers suggests that locus heterogeneity may exist for this disorder [7
In addition to the obvious bony changes, patients have extraskeletal manifestations, which include upper airway malformations and recurrent respiratory symptoms, conductive hearing loss, underdeveloped musculature, mental retardation, cardiac defects, and genitourinary malformations [7
Our case is typical of this syndrome with the exception of the urological manifestations, which are only briefly described in the literature. To date, of the few dozen male cases that have been reported worldwide, only approximately 32% [7
] have had some form of congenital obstructive uropathy [2
]. Although the most common urologic complication of the syndrome is urethral obstruction [7
], there is not a meticulous description of the symptoms or their treatment.
However, on reviewing the literature, an obstructive uropathy has been previously reported. A 10-year-old male patient, briefly described by Sauvegrain et al., presented with bilateral dilatation of the renal pelvises and ureters. Although the authors did not comment on the urethra, this anomaly suggests the presence of a lower urinary tract obstructive lesion [4
]. One patient, reported by Kassner et al., died from septic pyelonephritis due to hydronephrosis [8
]. The child described by Kanemura et al. had stenosis of the external urethral meatus, stricture of the membranous urethra, stenosis of the right ureterovesical junction, and bilateral hydronephrosis with hydroureters [9
]. Fitztimmons et al. also reported a male patient suffering from frontometaphyseal dysplasia. From the time of delivery, the patient suffered from posterior urethral valves and bilateral hydroureters with hydronephrosis. The valves were successfully treated by diathermy [2
]. An 11-year-old boy with frontometaphyseal dysplasia was described by Lee et al. as having bilaterally urinary tract malformation and chronic urinary tract infections. To improve his facial appearance, this patient's prominent supraorbital ridges were contoured by ostectomy. A urologic operation was performed simultaneously [10
]. Morava et al. described another male patient diagnosed with frontometaphyseal dysplasia who had recurrent hematuria. Cystourogram results suggested the presence of a mild constriction at the proximal urethra, which required treatment with antibiotics [11
This study indicates that obstructive lesions of the ureters and urethra commonly accompany frontometaphyseal dysplasia and should be specifically sought and excluded in individuals for whom the diagnosis is being considered. Our case represents a guide to how patients suffering from this rare syndrome may be approached to assess and correct functional and anatomical anomalies.
Before presentation to our department, the patient underwent a urodynamic evaluation elsewhere. From these results, our colleagues concluded that his main problem was neurogenic bladder dysfunction. They attributed this to his rare genetic syndrome, although Gorlin-Cohen syndrome has never been previously reported to be accompanied by neurological manifestations, and the patient appeared mentally and neurologically normal. Their suggestion was for the patient to undergo a permanent vesicostomy by the Mitrofanoff procedure to allow emptying of his bladder by self-catheterizations; urethral self-catheterizations were very difficult because of his anatomic malformations. After meticulous radiologic and endoscopic examination, this diagnosis proved to be incorrect, and the patient only required minor surgery to successfully treat his severe outflow obstruction.