Facial features in children with the 22q11 deletion syndrome

AIM: To find a pattern of the most typical facial features in children with the 22q11 deletion syndrome, which could serve as an aid in identifying patients with the syndrome. METHODS: In 80 children and adolescents with the 22q11 deletion syndrome, three investigators evaluated the facial features separately using frontal and profile photographs. A patient was considered to have a given feature if at least two of the evaluators agreed. RESULTS: The most common facial features found in at least 50% of the patients were malar flatness, fullness of eyelids (hooded eyelids), broad nasal bridge/tubular nose, broad/round nasal tip, round ears, thick/overfolded helix and slightly low-set ears. These were also the most common features when all agreed, although a considerable variation in the assessment by the three evaluators was observed. CONCLUSIONS: The 22q11 deletion syndrome is a differential diagnosis in children with a variety of symptoms and signs including congenital malformations, developmental delay and speech abnormalities. Almost all children with the syndrome show a characteristic pattern of minor facial variants, which can be difficult to recognise, unless specifically looked for. A systematic evaluation of facial features might help in identifying children with the syndrome.     

Coronary ostium occlusion by coronary cusp displacement in Williams syndrome

Williams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6‐year‐old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS.     

Rare clinical entity Perlman syndrome: Is cholestasis a new finding?

Perlman syndrome is a rare syndrome characterized by polyhydramnios, fetal overgrowth, facial dysmorphism, visceromegaly, nephroblastomatosis and predisposition to Wilms tumor. Here we report on a newborn with a prenatal history of polyhydramnios who presented with nephromegaly, hypotonia, macrosomia, facial dysmorphism, cholestasis and characteristic ultrasonographic and computed tomographic appearances of renal abnormalities that are observed with Perlman syndrome. Perlman syndrome is a rare entity with a high neonatal mortality rate. This is the first case in which cholestasis has been observed. Close follow‐up should be carried out for early detection of Wilms tumor.     

Sturge–Weber syndrome: From the past to the present

Sturge–Weber syndrome is a rare sporadic neurocutaneous syndrome the hallmark of which is a facial port-wine stain involving the first division of the trigeminal nerve, ipsilateral leptomeningeal angiomata and angioma involving the ipsilateral eye. Our understanding of the disease process has vastly improved since it was first described in 1879, with recent identification of an activating somatic mutation in the GNAQ gene found in association with both Sturge–Weber syndrome and non-syndromic facial port-wine stain. Sturge–Weber syndrome is marked by a variable but usually progressive course in early childhood characterised by seizures, stroke-like episodes, headaches, neurological and cognitive deterioration, hemiparesis, glaucoma and visual field defects. More recently, the increased prevalance of otolaryngological, endocrine and emotional–behavioural issues have been established. Neurophysiology and neuroimaging studies provide information regarding the evolution of changes in Sturge–Weber syndrome over time. Early recognition and aggressive management of symptoms remains cornerstone in the management of this syndrome. An international collaborative effort is needed to maximise our understanding of the natural history and response to interventions in Sturge–Weber Syndrome.     

Verbal bias in recognition of facial emotions in children with Asperger syndrome

Thirteen children and adolescents with diagnoses of Asperger syndrome (AS) were matched with 13 nonautistic control children on chronological age and verbal IQ. They were tested on their ability to recognize simple facial emotions, as well as facial emotions paired with matching, mismatching, or irrelevant verbal labels. There were no differences between the groups at recognizing simple emotions but the Asperger group performed significantly worse than the control group at recognizing emotions when faces were paired with mismatching words (but not with matching or irrelevant words). The results suggest that there are qualitative differences from nonclinical populations in how children with AS process facial expressions. When presented with a more demanding affective processing task, individuals with AS showed a bias towards visual-verbal over visual-affective information (i.e., words over faces). Thus, children with AS may be utilizing compensatory strategies, such as verbal mediation, to process facial expressions of emotion.     

3-M syndrome in two sisters

3-M syndrome is a rare, autosomal recessive dwarfing syndrome characterized by prenatal growth restriction, facial dysmorphism and absence of both microcephaly and mental retardation. The term 3-M syndrome originates from the common initial of the first three authors of the first report. The diagnosis is established by a combination of clinical history, clinical examination and radiographic findings. The present report shows two sisters whose facial features were slightly different from those usually reported. In addition, they presented with small nails and abnormal dermatoglyphics. The present report expands the phenotypic spectrum of 3-M syndrome.     

Congenital unilateral facial nerve palsy as an unusual presentation of BOR syndrome

Congenital facial nerve palsy (CFNP) is a rare condition that can be generally categorized as developmental or traumatic. Though trauma during birth is the most common cause, sometimes CFNP is observed in association with genetic syndromes and congenital hearing loss and structural anomalies of the middle and inner ear. CFNP is infrequently reported in association with branchio–oto–renal (BOR) syndrome. We present a case of a 4-day-old infant girl with a familial history of renal disease, who was hospitalized because of congenital unilateral facial palsy, which subsequently appeared to be a part of BOR syndrome and led to the diagnosis of congenital bilateral renal hypoplasia, renal failure, and secondary arterial hypertension. This case proves that sometimes rare manifestations of BOR syndrome may be one of the first signs of an underlying syndrome. Issues regarding patterns of BOR syndrome inheritability and expressivity that we encountered are also discussed. Patients with a familial history of BOR syndrome should be carefully inspected after birth, especially in suspected cases such as newborns with preauricular pits and/or facial nerve palsy.     

Evaluation of the maxillofacial morphological characteristics of Apert syndrome infants

Apert syndrome is a rare craniosynostosis syndrome characterized by irregular craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet. Previous studies analyzed individuals with Apert syndrome and reported some facial and intraoral features caused by severe maxillary hypoplasia. However, these studies were performed by analyzing both individuals who had and those had not received a palate repair surgery, which had a high impact on the maxillary growth and occlusion. To highlight the intrinsic facial and intraoral features of Apert syndrome, five Japanese individuals with Apert syndrome from 5 years and 2 months to 9 years and 10 months without cleft palate were analyzed in this study. A concave profile and a skeletal Class III jaw‐base relationship caused by severe maxillary hypoplasia were seen in all patients. The patients exhibited anterior and posterior crossbites possibly due to a small dental arch of Maxilla.     

Sturge–Weber syndrome without facial nevus: An unusual cause of neonatal seizures

Sturge‐Weber syndrome is a neurocutaneous syndrome characterised by facial port wine stain, ipsilateral leptomeningeal angioma and vascular eye abnormalities. We report a rare case of Sturge‐Weber syndrome without facial nevus presenting with neonatal seizures.     

Hemimegalencephalic variant of epidermal nevus syndrome: case report and literature review

The epidermal nevus syndrome (ENS) is an uncommon neurocutaneous disorder in which epidermal nevi are found in association with congenital abnormalities of the brain, eye, and/or skeleton. The association of epidermal nevi and neurologic abnormalities was comprehensively described by Schimmelpenning in 1957. Pavone et al. (1991) identified a homogeneous variant of ENS with hemimegalencephaly, gyral malformation, mental retardation, seizures and facial hemihypertrophy. A 13-year-old boy with the neurologic variant of ENS with hemimegalencephaly, facial asymmetry, febrile seizures and mental retardation is reported. Additionally, we performed a literature review using the search terms "epidermal nevus syndrome" and "hemimegalencephaly", including secondary sources of data such as reference lists of articles reviewed. We found 57 previously reported cases with the hemimegalencephalic variant of epidermal nevus syndrome, in which the most frequent associated features are severe epilepsy, in about half of cases with neonatal onset, mental retardation/developmental delay, ocular/visual involvement, and facial abnormalities.     

Serpentine fibula — polycystic kidney syndrome

A 5-year-old girl is reported with small stature, unusual facial appearance, polycystickidneys and elongated curved fibulae as the most impressive radiographic finding. From the close similarity with another girl described recently and discrepancies between these two patients and others with Melnick-Needles syndrome it is assumed that they may present a separate hitherto unreported entity or syndrome.     

Late-onset Lymphedema and Protein-losing Enteropathy with Noonan Syndrome

Noonan syndrome is characterized by facial dysmorphology, congenital heart disease and growth failure. Although it is also accompanied by deranged lymph-vessel formation, protein-losing enteropathy (PLE) with Noonan syndrome is rarely reported. We report clinical information about a boy with Noonan syndrome and late-onset lymphedema and PLE after standing for long periods of time during athletic practice sessions. The boy recovered from lymphedema and PLE after administration of 2.5 g of albumin followed by resting and raising his legs. They did not recur after he began walking again. Standing for long periods of time congested the lymph stream at the abdominal lymph vessel, whose formation is frequently disturbed in Noonan syndrome, and the increased pressure caused lymphedema and PLE. PLE is one of the clinical manifestations of Noonan syndrome.     

Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome

Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a condition characterized by variable combined immunodeficiency, developmental delay, facial anomalies and a variety of structural chromosomal rearrangements. Recently, aberrations at the molecular level have been described consisting of alterations in the methylation pattern of classical satellite DNA. To our knowledge 15 subjects have been described so far in the literature showing marked phenotypic variability. We report on two new patients with normal development and some peculiar clinical and immunological manifestations. All patients previously reported in the literature are reviewed.Conclusion The identification of these two cases among our hypogammaglobulinaemic patients suggests that ICF syndrome is not a rare disorder and it should be always taken into account in immunodeficient patients with facial abnormalities.     

Asphyxiating thoracic dystrophy with facial dysmorphism

Here it is reported a male newborn baby with features of asphyxiating thoracic dystrophy (ATD) with facial dysmorphism. The disproportionate rhizomelic short stature, narrow thorax, long fibulae, wide metaphysis and trident acetabule are consistent with diagnosis of ATD. In addition the baby had facial dysmorphism and broad thumbs and great toes similar to Oto-palato-digital syndrome type II (OPD II). The association of these features with ATD is not reported till date.     

Munchausen syndrome by proxy: definition of factitious bleeding in an infant by 51Cr labeling of erythrocytes.

The Munchausen syndrome by proxy is a phenomenon in which symptoms of a disease are fabricated by some person other than the patient. This report describes and 8-week-old infant with repetitive bleeding episodes, presumably originating from the upper respiratory tract. Extensive investigations, including angiography, several endoscopies under general anesthesia, and reinfusion of the infant's red cells labeled with 51Cr followed by pulmonary and upper airway scanning, failed to reveal the source of bleeding. Within two weeks after initiation of the 51Cr studies, radioactivity of facial blood from two separate bleeding episodes did not exceed background counts. Simultaneous examination of the infant's capillary blood, however, showed moderate to marked radioactivity. The Rh subtype of the facial blood was cc, whereas the infant's type was Cc. These findings indicated that the facial blood was factitious in origin. No further "bleeding" occurred after this information was presented to the parents. This case represents an unusual example of the Munchausen syndrome by proxy. Awareness of this entity can prevent potentially harmful investigations. Documenting its occurrence and sharing the information with parents in a nonaccusatory manner may prevent future harm to the patient.     

Microdeletion of 22q11 (CATCH 22) in children with conotruncal heart defect and extracardiac malformations

CATCH 22 is a medical acronym for cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia, and a variable deletion on chromosome 22q11. The deletion within the chromosome region of 22q11 may occur in patients with dysmorphologic and cardiological syndromes: DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face syndrome (CAFS). In this study, using N25 (D22S75) DiGeorge chromosome region probe. fluorescence in situ hybridization (FISH) analyses were performed on 32 patients with congenital heart diseases. Twenty-nine of 32 patients had conotruncal heart disease. A 22q11 deletion was detected in two patients (6.9%) of the 29 patients with conotruncal heart disease. One of our 22qdel (+) patients had unilateral facial nerve palsy. Although it is not a frequent finding, unilateral facial nerve palsy will be included among the symptoms of CATCH 22 syndrome. After careful clinical evaluation of patients with conotruncal cardiac anomalies, only syndromic cases should be screened for this deletion.     

Nocturnal lagophthalmos in children with urofacial syndrome (Ochoa): A novel sign

The urofacial syndrome is a rare condition that occurs in both genders and characterized by uropathy and facial abnormalities. Early diagnosis is crucial for the management and prognosis of urinary problems. Paradoxical inversion of facial musculature when smiling, giving an appearance of crying associated with severe urinary tract dysfunction is typical in these patients. Although facial signs and symptoms are generally ignored and shadowed by the dominant bladder symptoms, we have recently realized a unique but constant finding in majority of these patients, nocturnal lagophthalmos which is described as inability to close the eyelids during sleep. We report 15 patients with urofacial syndrome (Ochoa) whom mostly had admitted with major urological symptoms and 12 of the cases had nocturnal lagophthalmos. Lagophthalmos may lead to keratitis, corneal abrasion, infection, vascularization, and in extreme cases, ocular perforation, endophthalmitis and loss of the eye. Basic modalities like lubricant drops during the day and ointments at night are usually enough to protect the cornea from exposure keratopathy. In moderate to severe cases, overnight taping of the lid or the use of a moisture chamber might be necessary. Majority of our patients responded to basic therapy. Conclusion Nocturnal lagophthalmos is a novel symptom described in patients with urofacial syndrome. The pediatricians and urologists should be careful about this symptom to prevent eye damage and quality of life problems.     

Apert's syndrome with polymetatarsia]

Three cases of acrocephalosyndactyly with duplication of the first toe and presence of six well-individualized metatarsals are reported. This type of polysyndactyly should suggest the diagnosis of Carpenter syndrome, which is inherited on a recessive autosomal basis. However, in the three patients reported here, the facial dysmorphism was distinct from that seen in Carpenter syndrome and the syndactyly was more marked. The correct diagnosis therefore seems to be Apert acrocephalosyndactyly, a disease with dominant transmission. A mutation seems very likely and consequently the risk of recurrence in siblings is probably minimal.     

Cayler's cardio-facial syndrome. Apropos of 19 cases

Hypoplasia of the depressor angulae oris muscle can be detected in the crying newborn by an asymmetry of the facies, and it must be differentiated from facial palsy. Asymmetry of the facies during crying spells associated with a congenital cardiac abnormality constitutes the Cayler's cardiofacial syndrome. Nineteen cases of this syndrome are reported. A wide spectrum of congenital heart defects of varying severity was observed, ventricular septal defect being the most common along with frequent malformations involving systems and organs other than the heart.     

Update on hemangiomas and vascular malformations.

Hemangiomas and vascular malformations are frequently encountered in pediatric practice, especially hemangiomas and port-wine stains. These lesions may cause physical and psychological complications and it is important to recognize which lesions need to be treated and how. Great progress has been made in the classification of vascular anomalies. Angiogenesis and molecular genetics are areas of active research; recent findings relating to hemangiomas and vascular malformations are presented. New clinical features of hemangiomas are described, such as association of extensive facial hemangiomas with various malformations and the occurrence of Kasabach-Merritt phenomenon, not with common hemangiomas, but with other vascular tumors (Kaposiform hemangioendothelioma and tufted angioma). Interferon alfa is effective for treatment of complicated hemangiomas but may cause serious neurological side effects. It is to be hoped that early diagnosis of Sturge-Weber syndrome will soon be possible with new, noninvasive, functional imaging techniques. New issues surrounding pulsed dye laser therapy for port-wine stains are also discussed in this article.