Nasopalpebral lipoma-coloboma syndrome

An autosomal dominant dysplasia-malformation syndrome affecting seven individuals in one family is reported. The components of the syndrome include congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. It appears to be the second recorded example resulting from an autosomal dominant gene fully penetrant in both sexes.     

Macrocephaly with hamartomas: Bannayan-Zonana syndrome

Familial macrocephaly with mesodermal hamartomas is described as a distinct syndrome in nine individuals from four families. Constant manifestations include symmetrical macrocephaly without ventricular enlargement, mild neurological dysfunction, and postnatal growth deceleration. Speech and motor delays observed in all the children were usually well compensated by adulthood. Two children had mild mental retardation and seizures which may have been related to intracerebral hemorrhage in one. Mesodermal hamartomas were present in affected persons from all four families, with 60% of individuals manifesting only discrete lipomas and hemangiomas. More serious tumors, including intracerebral hemangiomas, hemangiomatous involvement of the bone, and aggressive lipomas occurred in 40%. Other findings that make it possible to delineate a recognizable syndrome include down-slanting palpebral fissures (66%), a high palate (67%), joint hyperextensibility (55%), pectus excavatum (22%), strabismus or amblyopia (33%), and prolonged drooling (44%). The Bannayan-Zonana syndrome is an autosomal-dominant trait with male predominance of affected individuals.     

The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: an in vivo confocal and histological study

The inner border of the eyelid margin is critically important for ocular surface integrity because it guarantees the thin spread of the tear film. Its exact morphology in the human is still insufficiently known. The histology in serial sections of upper and lower lid margins in whole-mount specimens from 10 human body donors was compared to in vivo confocal microscopy of eight eyes with a Heidelberg retina-tomograph (HRT II) and attached Rostock cornea module. Behind the posterior margin of the Meibomian orifices, the cornified epidermis stopped abruptly and was replaced by a continuous layer of para-keratinized (pk) cells followed by discontinuous pk cells. The pk cells covered the muco-cutaneous junction (MCJ), the surface of which corresponded to the line of Marx (0.2-0.3 mm wide). Then a stratified epithelium with a conjunctival structure of cuboidal cells, some pk cells, and goblet cells formed an epithelial elevation of typically about 100 μm initial thickness (lid wiper). This continued for 0.3-1.5 mm and formed a slope. The MCJ and lid wiper extended all along the lid margin from nasal to temporal positions in the upper and lower lids. Details of the epithelium and connective tissue were also detectable using the Rostock cornea module. The human inner lid border has distinct zones. Due to its location and morphology, the epithelial lip of the lid wiper appears a suitable structure to spread the tear film and is distinct from the MCJ/line of Marx. Better knowledge of the lid margin appears important for understanding dry eye disease and its morphology can be analysed clinically by in vivo confocal microscopy.     

Gorlin-Chaudhry-Moss or Saethre-Chotzen syndrome?

We report a 2-year-old girl with craniosynostosis, an ossification defect of the cranial vault, midface hypoplasia, low frontal hairline, anti-mongoloid slant of the palpebral fissures, ptosis of the lateral upper lids and high-arched narrow palate. There are additional findings fitting the Gorlin-Chaudhry-Moss syndrome, such as hypoplasia of the labia majora, hypoplasia of the distal phalanges of fingers and toes and conductive hearing loss, but hypertrichosis and dental anomalies are missing, which were described in the four females previously reported with the probably autosomal recessive Gorlin-Chaudhry-Moss syndrome. Since the autosomal dominant Saethre-Chotzen syndrome may show similar craniofacial features, short fingers with non-obligatory cutaneous syndactyly, and ossification defects of the cranial vault, the Saethre-Chotzen syndrome should also be considered in our patient.     

Human eye movements associated with blinks and prolonged eyelid closure

Eye movements associated with eyelid closure were recorded in human subjects with search coils, embedded in self-adhering scleral annuli, in a magnetic field. In contrast to classical notions, voluntary as well as reflex blinks were consistently accompanied by transient downward and nasalward movements of both eyes with amplitudes 1-5 degrees. These eye movements had a shorter duration than the upper lid movements, and the shapes of the spatial trajectories of eye and lid movements were not similar. The trajectory of the eye movements was only modestly affected by gaze eccentricities up to 15 degrees; there was a tendency for the downward component to be enhanced by looking upward, and vice versa. Restraining of the lids of one eye in the open or closed position did not significantly alter the eye movements during (attempted) blinks. Velocity-amplitude-duration relations of the down- and upward components were similar for the same eye before and after closure and for the closed eye and the contralateral unrestrained eye. The velocity-amplitude-duration characteristics of saccades were also unaffected by prolonged closure of the lids of one eye. Prolonged, voluntary closure of the lids was followed by a slow, tonic ocular deviation, which was consistently upward in half of the subjects and consistently downward in the other half. Additional horizontal components were highly variable even within subjects. In one subject the downward deviation was converted into upward deviation when lid closure was mechanically impeded. We conclude that elevation of the eye ball (Bell's phenomenon) does not occur during short blinks and only in about half of the subjects during voluntary unrestrained prolonged lid closure. Our evidence does not support the possibility that the transient eye movements during blinks are caused primarily by a mechanical interaction between the lids and the eye (or the scleral annulus). More likely, they are a secondary effect of an active cocontraction of extraocular muscles that primarily results in retraction of the eye.     

Genetic aspects of immotile cilia syndrome

The genetics of the immotile cilia syndrome has been analyzed in a series of 46 affected individuals from 38 families. Both sexes were equally affected: there were 20 males and 26 females in this series. All patients had upper and lower respiratory disease with chronic sinusitis, otitis, and chronic cough from early childhood. Bronchiectasis was common in older children and adults. Situs inversus occurred randomly, affecting 11 males and 15 females. Biopsies of nasal and bronchial mucosa from these subjects have been investigated by electron microscopy and identified as having specific ultrastructural defects of respiratory tract cilia including deficiencies in outer dynein arms (19), inner dynein arms (3), both inner and outer dynein arms (15), radial spoke defect (5); and microtubular transposition anomaly (4). Segregation analysis of proband sibships was consistent with autosomal recessive inheritance. However, the different ultrastructural defects that underly the immotile cilia syndrome involve presumably different genetic determinants, and the different types have not been analyzed separately. Examination of paternal age and birth order gave no evidence of new autosomal dominant mutation in the series.     

Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis

Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two hamartoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia. PTEN is a tumour suppressor and dual-specificity phosphatase which affects apoptosis via its lipid phosphatase activity in the phosphoinositol-3-kinase and AKT pathway as well as inhibiting cell spreading via the focal adhesion kinase pathway. CS and BRR share some features, such as hamartomas and lipomatosis. To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or BRR. Five had Proteus syndrome and one, a Proteus-like syndrome. When germline DNA and DNA from at least one involved tissue per case were examined for PTEN mutations, only the Proteus-like patient was found to harbour a germline R335X mutation. Interestingly, a lipomatous mass, an epidermoid naevus and arteriovenous malformation tissue, all of which were sampled from physically distinct sites, were all found to carry a second hit R130X mutation on the allele opposite the germline R335X. Both mutations have been described in CS and BRR. We postulate that the second hit, R130X, occurred early in embryonic development and may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future.     

Acrocallosal syndrome: report of a Brazilian girl.

We report on a Brazilian girl born to nonconsanguineous parents and presenting with frontonasal dysostosis, callosal agenesis, abnormal upper lids, cleft lip/palate, redundant skin in the neck, grooved chin, and bifid thumbs. Major diagnostic criteria present in this patient are related to the acrocallosal syndrome. The clinical and major nosologic aspects of this condition are discussed.     

Acrocallosal syndrome: Report of a Brazilian girl

We report on a Brazilian girl born to nonconsanguineous parents and presenting with frontonasal dysostosis, callosal agenesis, abnormal upper lids, cleft lip/palate, redundant skin in the neck, grooved chin, and bifid thumbs. Major diagnostic criteria present in this patient are related to the acrocallosal syndrome. The clinical and major nosologic aspects of this condition are discussed. © 1992 Wiley-Liss, Inc.     

Short bi-iliac distance in prenatal Ullrich-Turner syndrome

The purpose of the present study is to evaluate the bi-iliac distance and the caudo-cranial position of the iliac bones in Ullrich-Turner syndrome (UTS) fetuses compared to recently published standards for normal fetuses. Whole-body radiographs in antero-posterior projections of 24 UTS fetuses (crown-rump lengths, 106-220 mm) were included in the study. From each radiograph, two horizontal (outer and inner bi-iliac distances) and two vertical (caudo-cranial) positions compared to the vertebral column were measured to estimate the position of the iliac bones. The present investigation revealed that both the outer and inner bi-iliac distances were significantly shorter in UTS fetuses than in normal fetuses. We also found that for the inner bi-iliac distance, the growth rate in UTS fetuses was significantly lower than in normal fetuses. This finding suggests not only a lesser growth but also a different growth pattern compared to normal fetuses. Regarding the caudo-cranial position of the iliac bones compared to the lower vertebral column, there was no significant difference for the lower caudo-cranial position, but the upper caudo-cranial position was significantly lower in UTS fetuses than in normal fetuses. The bi-iliac distance and the iliac bone position have not previously been described in Ullrich-Turner syndrome fetuses.     

Kabuki syndrome: Clinical data in 20 patients, literature review, and further guidelines for preventive management

The Kabuki syndrome, or Niikawa-Kuroki syndrome, is a clinically recognizable syndrome of unknown etiology. Clinical findings include early hypotonia, joint laxity, developmental delay, facial dysmorphism, persistent fetal fingertip pads, cleft palate, hypodontia, lip nodules, heart defects, and a variety of other structural defects. Behavior in general is social and pleasant. In collaboration with the Dutch Kabuki Network, we evaluated the medical data of 20 individuals diagnosed with the syndrome and compared them with data from the literature. In our literature review we used convincing cases only. Frequent findings in the oral region are under-reported in the literature: apart from the cleft palate (in about 50%), hypodontia with predominantly absence of the upper lateral incisors, and a full lower lip with symmetrical nodules, or (in a minority) lip-pits are frequent findings. Also under-reported is the presence of a thickened nuchal fold during pregnancy and hydrops in the neonatal period. Clinical recognition in the neonate is difficult. Towards early puberty acute and serious weight excess has been experienced. We suggest that a cytogenetic abnormality should be ruled out in all cases. We provide further guidelines for preventive management.     

An unusual cardiomelic syndrome

We report on a patient with pre- and postnatal growth retardation, bilateral symmetrical ulnar agenesis with monodactyly, atrial septal defect, two ventricular septal defects, Wolff-Parkinson-White conduction abnormality, and abnormal configuration of the pancreas. Although she had some facial features reminiscent of the Brachmann-de Lange syndrome, relatively normal head size and motor development indicate a distinct syndrome.     

Otofaciocervical syndrome: a sporadic patient supports splitting from the branchio-oto-renal syndrome

A sporadic patient with OFC syndrome is described. Distinguishing features were a long face with narrow nose, high arched palate, prominent and dysmorphic ears, long neck, sloping shoulders and clavicles, winged, low, and laterally set scapulae, tetralogy of Fallot, and deafness secondary to cochlear malformation. Some features present in the original family, including lateral cervical fistulae, have suggested that OFC syndrome could be a variant of BOR syndrome. The absence of preauricular tags, lacrimal duct stenosis, and renal malformations, and the presence of distinct facial and radiographic findings and markedly downward sloping shoulders in the present patient support OFC syndrome being a unique, clinically recognisable entity.     

Adults with Down''s syndrome: the prevalence of complications and health care in the community

BACKGROUND: Individuals with Down's syndrome are predisposed to a variety of medical conditions which can impose an additional, but preventable, burden of secondary disability. Although there are guidelines for health checks and medical management of children with Down's syndrome, the needs of adults are relatively neglected. AIM: To determine the prevalence of common medical problems in adults with Down's syndrome, and to assess current practice regarding medical surveillance of these patients. DESIGN OF STUDY: Detailed notes analysis. SETTING: Data were obtained from the primary care records of adults with Down's syndrome living in the Newcastle upon Tyne and Gateshead areas. METHOD: Case notes were reviewed to obtain details regarding complications and to determine the frequency of medical surveillance of individuals with Down's syndrome. RESULTS: Complications such as hypothyroidism, celiac disease, and obesity occur more frequently in adults with Down's syndrome than previous paediatric prevalence studies suggest. Surveillance of common complications that occur in individuals with Down's syndrome is infrequent. In this study, 48% of adults with Down's syndrome had not seen a doctor in the previous 12 months and 33% had not had a medical assessment in the previous 3 years. CONCLUSION: Many individuals with Down's syndrome do not have access to regular healthcare checks, despite the high frequency of common medical complications in adult life. Debate regarding the practicality and relevance of introducing regular health checks is warranted.     

Bilaterally cleft lip,limb defects,and haematological manifestations: Roberts syndrome versus TAR syndrome

We report on a 13-year-old patient followed since birth. He is the only offspring of young, non-consanguineous German parents. His mother has an isolated left cleft of lip and a cleft palate. At birth, our patient presented with bilaterally cleft lip/cleft palate, phocomelia of upper limbs with normal hands, and mild symmetrical deficiencies of the long bones of the lower limbs. Haematological evaluation demonstrated a leukaemoid reaction during a urinary tract infection as well as intermittent thrombocytopenia and episodes of marked eosinophilia during the first two years of life. Intellectual development has been normal. Comparison with two similar cases from the literature suggests a non-random phenotypic overlap of Roberts syndrome (MIM 268300) and TAR syndrome (MIM 274000). Such clinical constellations may be key observations to understand the genetic relationship of Roberts syndrome and TAR syndrome in future phenotype–genotype correlations. Am. J. Med. Genet. 79:155–160, 1998. © 1998 Wiley-Liss, Inc.     

Dominant syndrome with isolated cryptophthalmos and ocular anomalies.

We report on a mother and daughter with nonsyndromal cryptophthalmos. Both patients have additional ocular anomalies, including microphthalmia, retinal dysplasia, and Peters anomaly. The periocular and lid changes seen in these individuals are distinct from those seen in typical cryptophthalmos. The apparent dominant mode of inheritance in this family distinguishes this condition from autosomal recessive isolated cryptophthalmos and from the Fraser or cryptophthalmos syndrome.     

Aicardi syndrome,metastatic angiosarcoma of the leg,and scalp lipoma

An infant girl with Aicardi syndrome, scalp lipomas, and angiosarcoma of a limb is reported. The cavernous hemangioma of the leg was benign when biopsied at age 5 months but became malignant at 11 months. Angiosarcoma caused multiple distant metastases which were evident at autopsy at age 19 months. This is the first case of Aicardi syndrome associated with lipoma and metastatic angiosarcoma. © 1993 Wiley-Liss, Inc.     

Dominant syndrome with isolated cryptophthalmos and ocular anomalies

We report on a mother and daughter with nonsyndromal cryptophthalmos. Both patients have additional ocular anomalies, including microphthalmia, retinal dysplasia, and Peters anomaly. The periocular and lid changes seen in these individuals are distinct from those seen in typical cryptophthalmos. The apparent dominant mode of inheritance in this family distinguishes this condition from autosomal recessive isolated cryptophthalmos and from the Fraser or cryptophthalmos syndrome. © 1992 Wiley-Liss, Inc.     

Short bi‐iliac distance in prenatal Ullrich‐Turner syndrome

The purpose of the present study is to evaluate the bi‐iliac distance and the caudo‐cranial position of the iliac bones in Ullrich‐Turner syndrome (UTS) fetuses compared to recently published standards for normal fetuses. Whole‐body radiographs in antero‐posterior projections of 24 UTS fetuses (crown‐rump lengths, 106–220 mm) were included in the study. From each radiograph, two horizontal (outer and inner bi‐iliac distances) and two vertical (caudo‐cranial) positions compared to the vertebral column were measured to estimate the position of the iliac bones. The present investigation revealed that both the outer and inner bi‐iliac distances were significantly shorter in UTS fetuses than in normal fetuses. We also found that for the inner bi‐iliac distance, the growth rate in UTS fetuses was significantly lower than in normal fetuses. This finding suggests not only a lesser growth but also a different growth pattern compared to normal fetuses. Regarding the caudo‐cranial position of the iliac bones compared to the lower vertebral column, there was no significant difference for the lower caudo‐cranial position, but the upper caudo‐cranial position was significantly lower in UTS fetuses than in normal fetuses. The bi‐iliac distance and the iliac bone position have not previously been described in Ullrich‐Turner syndrome fetuses. © 2002 Wiley‐Liss, Inc.