Facial morphometrics in the identification of gene carriers of X-linked hypohidrotic ectodermal dysplasia.

Roentgenographic measurements and morphometric analysis were employed in the investigation of contrasting patterns of craniofacial variation between normal individuals and those affected by X-linked hypohidrotic ectodermal dysplasia (HED). The research objective was to identify and describe the facial characteristics of heterozygous gene carriers who show minor expression of the disorder. In this study of 13 HED families with 16 affected males, 12 carriers, and 12 normal individuals, affected individuals had at least 3 of the following 4 clinical signs and symptoms: a) hypodontia, b) hypohidrosis, c) hypotrichosis, and d) clinically distinct facial physiognomy. By contrast, the gene carriers manifested only one or 2 or none of the 4 clinical manifestations. In a preliminary comparison of gene carriers vs. normal individuals, we have generated 2 discriminant functions (each based on 3 facial measurements taken either from the lateral or frontal cephalograms). These 2 functions correctly diagnose 100% of the gene carriers and normal HED relatives. Facial anomalies characteristic of the gene carriers were 1) abnormally narrow and short maxillary width and palatal depth dimensions; 2) very small and retrusive malar and maxillary regions; 3) markedly reduced lower facial depth, height and width dimensions; 4) small head height, prominent forehead, and high-set orbits; 5) a generalized, symmetric reduction of the whole craniofacial complex.

Facial dysmorphology, roentgenographic measurements, and clinical genetics.

Roentgenographic measurements are used in the facial diagnosis of a male patient (proband) and his mother with unusual craniofacies. Twenty-four measurements (from both the PA and LA x-ray headplates) defining the major anatomic areas of the head and face were chosen as the overall descriptors for the characterization and recognition of craniofacial pattern profile (CFPP). The measurements were transformed into Z-scores. By using the sigma z (i.e., standard deviation of the z-scores) value, the CFPP deviations were estimated. The proband and mother have aberrant, i.e., dysmorphic, craniofacial pattern profiles. The proband's CFPP is highly stable at two successive ages (6 and 13 years, respectively); only the cranial base and palatal dimensions are becoming increasingly abnormal and asymmetric. Familial as well as syndromic CFPP similarities were assessed. Results of correlation coefficients rz demonstrate a significantly high level of CFPP similarity between the proband and mother. This strongly suggests that the two are the carriers of the same genetic syndrome. Unusual syndrome-specific facial features shared by the two include abnormally large midface, very high-set and widely placed eyes, retrusive and asymmetric upper alveolar region, very small malar bones, and long mastoid processes.

Craniofacial pattern profile (CFPP) evaluation of facial dysmorphology in a familial syndrome with corneal anesthesia and multiple congenital anomalies.

Roentgencephalometric findings are presented for a family with an unusual facial morphology. Twenty measurements defining the size and shape of major anatomic areas of the head and face were taken. The measurements were transformed into Z-scores. Using the sigma z (i.e., standard deviation of the Z-scores) value, an estimate of craniofacial pattern deviation from the norms was made for each family member. All members of this family have highly aberrant, i.e., dysmorphic, craniofacial pattern profiles. Familial as well as syndromic craniofacial similarities vs. dissimilarities between Z-score values of pairs of family members were assessed by the Pearson's correlation coefficient rz. Results of correlation coefficients demonstrate a high level (far in excess of the expected value of rz 0.50) of craniofacial pattern profile (CFPP) similarity between sibs and between sibs and their mother. This strongly suggests that the two sibs and their mothers are the carrier of the same genetic syndrome.

Congenital corneal anesthesia with retinal abnormalities, deafness, unusual facies, persistent ductus arteriosus, and mental retardation: a new syndrome?

Two sibs who had hypesthetic corneas, absence of the peripapillary choriocapillaris and retinal pigment epithelium, sensorineural hearing loss bilaterally, persistent ductus arteriosus, moderate mental retardation, and unusual facial appearance are described. Their mother had mild to moderate sensorineural hearing loss, retinal changes and similar facial features. The differential diagnosis is discussed. We believe this is a clinically distinct syndrome with autosomal dominant inheritance.

Stickler syndrome: a cephalometric study of the face.

A lateral roentgencephalometric study to compare the facial morphology of 21 affected and 18 normal members of 8 families with the Stickler syndrome (SS) was undertaken. The affected individuals exhibited two or more of the following four clinical symptoms: (a) flat midface, (b) cleft palate, (c) eye problems, and (d) arthropathy. The diagnostic facial features of the affected individuals as a group were found to be markedly shortened cranial base length, midfacial depth and height, maxillary depth, and mandibular depth, but significantly larger total and lower facial height dimensions. Facial morphology is highly characteristic for the Stickler syndrome. An application of two discriminant function equations (each based on four cephalometric measurements) to our data correctly identified 84.6 to 89.7% of the affected and normal SS family members. These discriminant function equations should be of considerable aid in the clinical diagnosis of the SS patient prior to the onset of symptoms.