American Journal of Medical Genetics 41:102-104 (1991)
Brief Clinical Report
Hypomandibular Faciocranial Dysostosis: Report of an Affected Sib and Follow-Up
R. Neil Schimke, Katherine S. Claflin, John H. Seguin, Timothy L. Bennett, Brent E. Finley, Lenna M. Levitch, and Ward M. Newcomb Departments of Pediatrics (R.N.S., K.S.C., J-H.S.) and Obstetrics-Gynecology (T.L.B., B.E.F., L.M.L.), Kansas University Medical School, Kansas City, Kansas; Hays Pathology Laboratory, Hays, Kansas (W.M.N.)
Hypomandibular faciocranial dysostosis is a condition heretofore described only in a sin- gle case. We report the birth of an affected sister along with follow-up information on the initial surviving patient. While a primary er- ror in neural crest development was postu- lated in this syndrome, subsequently discov- ered anatomical abnormalities suggest a more complex pathogenesis.
KEY WORDS: Craniosynostosis, gingival fu- sion, hypoglossia, tracheal dysgenesis, autosomal reces- sive inheritance
INTRODUCTION In 1988, Neidich et al. reported on a girl with unusual
abnormalities mostly of first branchial arch derivatives. Aglossia was suspected. The mandible was nearly ab- sent, and the maxilla and zygomatic arches were severely hypoplastic. Coronal craniosynostosis was present. The condition was termed hypomandibular fac- iocranial dysostosis by Gorlin et al. . While there was no initial evidence that the condition was heritable, a similarly affected sib subsequently has been born. We report follow-up information on the first sib along with the data pertinent to her more severely affected sister.
CLINICAL REPORT Patient 1
The birth and early development of this now 4%- year-old child was recorded elsewhere [Neidich et al., 19881. Briefly, the child was born at 36 weeks of gesta- tion after a pregnancy complicated by polyhydramnios.
Fkceived for publication October 15,1990; revision received Jan- uary 14, 1991.
Address reprint requests to Dr. R. Neil Schimke, Kansas Univer- sity Medical Center, 39th and Rainbow Boulevard, Kansas City, KS 66103.
This paper was presented in part a t the 11th Annual David W. Smith Workshop on Malformations and Morphogenesis, Lex- ington, KY August 5-8, 1990.
0 1991 Wiley-Liss, Inc.
At birth she had brachycephaly with coronal synostosis, shallow orbits and hypoplastic superior orbital ridges, absence of the mandible save for the anterior portion, hypoplastic maxillae and zygomatic arches, and essen- tially an absent palate. The lips were tightly pursed and protruded. There appeared to be a persistent buccal- pharyngeal membrane, and what remained of the man- dible was fused to the maxilla. The nose was short and nares anteverted, and the ears were slightly low-set. A right optic nerve coloboma and an atrial septa1 defect completed the clinical picture. A tracheostomy and feed- ing gastrostomy were necessary.
Multiple operations were performed over the ensuing months. The child, now 4%, was found to have a hypo- plastic tongue at the time of reconstructive surgery and now can consume liquids and pureed foods orally. Her current height and weight are a t the 75 centile, despite the permanent tracheostomy, bronchomalacia, and re- current pulmonary infections. She is severely develop- mentally delayed, but communicates with her parents and sibs via rudimentary sign language (Fig. 1).
Patient 2 The parents were advised that the risk for a subse-
quently affected child was finite but probably small, although no similar cases were available for compari- son. The mother became pregnant, and presented with polyhydramnios at 32 weeks gestation. A sonogram showed a fetus with facial findings identical to those of patient 1 (Fig. 2). The membranes ruptured pre- maturely at 35 weeks of gestation and a C-section was performed with delivery of 2,660 g girl.
A tracheostomy was performed with difficulty be- cause a segment of the trachea was atretic. The facial appearance of the infant was identical to that of her sister (Fig. 3A,B). She had bilateral optic nerve hypo- plasia and severe bilateral choanal stenosis. No heart defect was recognized. Later, a gastrostomy tube was placed and a persistent ductus arteriosus was ligated. The hospital course was complicated by lactose intol- erance, ventilator dependence with intermittent hyper- carbia, staphylococcal pneumonitis, and the need for repeated dilatation of the trachea distal to the tracheos- tomy site. Following parental wishes, the child was dis- charged to a local hospital and then home on a ventila-
Hypomandibular Faciocranial Dysostosis in Sibs 103
Fig. 1. A portrait photo of patient 1, age 3 years.
tor. The child continued to do poorly and died at age 6 months.
Only a limited autopsy was allowed. The prosecutor noted the obvious facial abnormalities and a persistent bucco-pharyngeal membrane. Behind the membrane, the gingivae were fused and the hard and soft palate were widely cleft. A tongue remnant was present. The epiglottis was rudimentary, enclosing only a slit-like primitive larynx (glottis) without associated laryngeal cartilage. The upper trachea was narrow and ended blindly 1 cm below the larynx. A dense strand of connec- tive tissue extended 4.5 cm from this blind pouch to a point where the tracheal lumen was present. No tra-
Fig. 2. Enlarged view of the sonographic profile of patient 2 in utero. Note the pursed lips and upturned nose. Compare with Figure 3B.
cheal cartilage was identified at any level, and the tra- chea, carina, and primary bronchi were noted to collapse when probes were removed. Both lungs showed periph- eral atelectasis with central bronchiolar dilatation, the latter giving the lungs a honeycombed appearance. The remainder of the autopsy was unremarkable.
Fig. 3. (A) Patient 2 shortly after birth (frontal); (B) patient 2 shortly after birth (profile). The face is virtually identical to that of patient 1, especially as a newborn infant [see Neidich et al., 19881.
104 Schimke et al.
DISCUSSION The condition affecting the 2 sibs appears to be
unique. The only case that is remotely similar was re- corded by Kittur et al. 119831, but that patient, an iso- lated case, had congenital fusion of apparently normal jaws and a normal tongue. While both mandible and maxilla were hypoplastic and malformed in the present patients, the essentially normal placement of the ears excludes a diagnosis of agnathia or otocephaly.
Neidich et al.  postulated a defect in neural crest development as possibly being responsible for the anomalies in patient 1, especially those elements de- rived from the first branchial arch. However, the poste- rior root of the tongue, present in both sibs, is derived from the third arch. The epiglottis (third and fourth arches) and the larynx and tracheal cartilages (fourth and subsequent arches) were also malformed or absent. The trachea and lungs are derived from the respiratory diverticulum which arises from the caudal floor of the pharynx. The precise cellular ontogeny of this structure is not known for certain, but neural crest elements have not been recognizably implicated. The peculiar discon- tinuity of the trachea in patient 2 is puzzling. Since it was not accompanied by esophageal atresia or a tra- cheoesophageal fistula, incomplete division of foregut derivatives cannot reasonably be implicated. The lar- ynx normally ends blindly until about 10 weeks of gesta-
tion because of rapid proliferation of the laryngeal epithelium. Thereafter recanalization takes place with the development of the laryngeal ventricles and the vocal cords. While incomplete recanalization usually results in a laryngeal web, a more severe lesion could conceivably lead to persistent sublaryngeal stenosis. Alternatively, the abnormality could be a disruption secondary to a vascular event, but the extensive involve- ment of the remainder of the airway suggests that the developmental defect in the larynx and trachea was a true malformation, the upper and lower segments differ- ing only in relative degree of severity.
Prometaphase banding of the chromosomes of the sur- viving sib showed no abnormalities at the 850 band level. Since sisters were affected, it appears that hypo- mandibular faciocranial dysostosis is an autosomal re- cessive trait.
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Moore KL (1988): The Developing Human, 4th ed. Philadelphia: WB Sanders , pp 207-212.
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