The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory obstruction, and in some cases, cleft palate. A causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated gene expression, precise cellular processes, pathogenesis, and PR-associated anomalies are documented. This review presents the current understanding of PR phenotypes, the proposed pathogenetic processes underlying them, select genes associated with PR, and available animal models that could be used to better understand the genetic basis and phenotypic variation of PR.

Pierre Robin sequence (PRS) or anomalad, a well-recognized presentation, is the association of the first brachial arch malformation. It presents with a classic triad of micrognathia, glossoptosis, and cleft palate. In a neonate with a complete cleft palate, problems with feeding are commonly encountered. Presented here are two cases with PRS in whom palatal obturators were constructed.

We report the first clinical case of a term infant with findings suggestive of lumbocostovertebral syndrome and VACTERL association. Renal agenesis was suspected by prenatal ultrasound, and at birth clinical findings included a large abdominal wall hernia, imperforate anus, vestibular fistula, absent right rib, vertebral anomalies, tethered cord, syringomyelia, and two small sacral dimples.

Otocephaly, characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia, is an extremely rare anomalad, identified in less than 1 in 70,000 births. The malformation spectrum is essentially lethal, because of ventilatory problems, and represents a developmental field defect of blastogenesis primarily affecting thefirst branchial arch derivatives. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. Polyhydramnios may be the presenting feature, but prenatal diagnosis has been uncommon. We present five new cases of otocephaly, the largest published series to date, with comprehensive review of the literature and an update of research in the etiopathogenesis of this malformation complex. One of our cases had situs inversus, and two presented with unexplained polyhydramnios. Otocephaly, while quite rare, should be considered in the differential diagnosis of this gestational complication.

The authors address the problem of why the cleft lip anomalad is not mentioned even once in the Talmud, which contains detailed reports of numerous other forms of pathology and congenital anomalies. It also attempts to define the Sandal deformity, one of the most common congenital anomalies mentioned in the Talmud. It is assumed that cleft lip, the most common major facial defect, existed at the time of the Talmud. It is proposed that the Sandal deformity was actually made up of a number of entities grouped together because of a theorized common etiology, and that the cleft lip entity is included in the Sandal anomalad. This deformity, in its various forms, included, besides cleft lip, aborted tissue and products of gestation. They are all related to the common etiology of a twin gestation during which one fetus presses against the other causing the deformity. The Sandal was noted to look like the Sandal fish or sole, for which it is named. When photos of the Sandal fish and the cleft lip deformity are compared, a similarity is seen. In addition, this deformity apparently was thought to be fatal, and none of these babies survived. It is theorized that cleft lip babies were allowed to die because they were considered nonviable in the eyes of Jewish law. Supporting evidence for the ideas presented by the authors is derived from the talmudic texts and commentaries. If the Sandal does indeed include the cleft lip entity, the citation in the Mishnah (70-200 AD) makes it the earliest historical reference to the cleft lip deformity.

In 1952, Wildervanck described the first case of what he called the Cervico-Oculo-Acoustic (COA) syndrome, which comprises Klippel-Fetl anomalad (congenitally fused cervical vertebrae), congenital deafness and Duane's retraction syndrome (abducen's paralysis and retraction on adduction). Since the first case was reported, there have been more reports describing this triad, either completely or incompletely. A further case of this syndrome with CSF leakage is reported here and exploratory tympanotomy was performed. Abnormalities of both inner and middle ear were found. In addition, MRI and CT scan of the head revealed an abnormal cerebellum which is the second case reported in the world. And a review of literature concerning this syndrome is also presented here.

The glossoptosis and micrognathia associated with Pierre Robin anomalad can make tracheal intubation by conventional laryngoscopy quite difficult. Lighted stylets may be helpful in the successful intubation of infants with this anomalad, but those currently available that are small enough to accommodate 3.0 mm ID tracheal tubes have two major drawbacks limiting their utility: an insufficiently rigid stylet component and a nonadjustable, overly bright light. We describe a lighted stylet that can be easily assembled in the operating room which overcomes these problems and allowed us to successfully intubate a six-day-old with severe Pierre Robin anomalad.

The glossoptosis and micrognathia associated with Pierre Robin anomalad can make tracheal intubation by conventional laryngoscopy quite difficult. Lighted stylets may be helpful in the successful intubation of infants with this anomalad, but those currently available that are small enough to accommodate 3.0 mm ID tracheal tubes have two major drawbacks limiting their utility: an insufficiently rigid stylet component and a nonadjustable, overly bright light. We describe a lighted stylet that can be easily assembled in the operating room which overcomes these problems and allowed us to successfully intubate a six-day-old with severe Pierre Robin anomalad.

Ectodermal dysplasia is a heterogeneous disorder that includes a constellation of congenital malformations occasionally associated with mild to moderate immune dysfunction. In this report, we describe a female infant with ectodermal dysplasia who was found to have thymic hypoplasia but no other phenotypic features of the DiGeorge anomalad. She experienced Candida parapsilosis sepsis at 1 week of age and a skin infection with Mycobacterium chelonii at 6 months. The numbers of blood B cells were normal and serum immunoglobulins normal to slightly reduced, but serum antibody responses of all immunoglobulin isotypes to protein immunogens were absent. Blood T cells were profoundly reduced and proliferative responses of T cells to mitogens were blunted. In contrast, there was an increased number of natural killer (NK) cells and increased NK activity in the blood. Over the first year of life, some of the immunodeficiencies resolved. Although the numbers of blood T cells (17% of total lymphocytes) remained low, proliferative responses to mitogens normalized and specific antibody responses improved. It seems likely that the thymic hypoplasia in this case was due to a paucity of ectodermal elements in the developing thymus, and that the immune defects were largely secondary to that event. In that respect, this human model of ectodermal dysplasia and thymic hypoplasia resembled the ectodermal/thymic defects found in the nude mouse.