Cryptophthalmos, dental and oral abnormalities, and brachymesophalangy of second toes: new syndrome or Fraser syndrome?

We report on an 8-year-old Thai girl with bilateral complete cryptophthalmos, facial asymmetry, delayed bone age, brachymesophalangy and medial deviation of the second toes, and dental anomalies. The dental anomalies consist of delayed dental development, congenital absence of the second premolars, microdontia of the deciduous molars. A fibrous band of the buccal mucosa was found. Dental anomalies are rare among patients with Fraser syndrome. They have not been reported in either isolated or other syndromic cryptophthalmos. The oral manifestations and brachymesophalangy of the second toes found in our patient may represent newly recognized findings associated with cryptophthalmos or they may represent a newly recognized syndrome.     

Digital anomalies,microcephaly, and normal intelligence: New syndrome or Feingold syndrome?

We present four patients—two boys and their mother and an unrelated girl—with microcephaly, normal intelligence, and digital abnormalities. The hand abnormalities are characterized by brachydactyly with radial clinodactyly of the fourth and fifth fingers, ulnar clinodactyly of the second fingers, and an increased space between the second and third fingers associated with an abnormal palmar crease that extends to the ulnar border. The foot abnormalities include short toes with syndactyly of the fourth and fifth toes. The mother has normal intelligence, and her sons and the unrelated girl have normal development. Although similar digital abnormalities, microcephaly, and normal intelligence were described by Feingold in patients with gastrointestinal atresia, we think that our patients' findings represent a different condition. The most likely mode of inheritance is autosomal dominant. The clinical recognition of this syndrome will allow for appropriate genetic counseling as well as provision of information on natural history, i.e., normal intelligence. Am. J. Med. Genet. 69:240–244, 1997. © 1997 Wiley-Liss, Inc.     

Severe limb abnormalities: Nievergelt or new syndrome?

Since the characteristic mesomelic limb abnormalities of the autosomal-dominant Nievergelt syndrome (NS) may be casually nonspecific, we are unsure whether our patient with these abnormalities but also with severe, symmetrical hand and foot anomalies has an unusual form of Nievergelt syndrome or a previously apparently undescribed syndrome. This infant's condition could represent an autosomal-dominant new mutation, or an autosomal or X-linked recessive disorder. Am. J. Med. Genet. 70:48–51, 1997. © 1997 Wiley-Liss, Inc.     

Vascular abnormalities in Adams-Oliver syndrome: Cause or effect?

We describe a young girl diagnosed with the Adams-Oliver syndrome (AOS) associated with double outlet right ventricle, portal hypertension, and pulmonary hypertension. We hypothesize that a congenital vascular abnormality is the underlying pathogenesis and that the cutaneous defects characteristically seen in AOS represent the most common manifestation of this. We suggest that AOS should not merely be considered a syndrome consisting of aplasia cutis congenita and terminal transverse limb defects but rather a constellation of clinical findings resulting from an early embryonic vascular abnormality. Am. J. Med. Genet. 82:49–52, 1999. © 1999 Wiley-Liss, Inc.     

Polyvalvular heart disease with joint hypermobility,characteristic facies,and particular skin abnormalities: New cases of “polyvalvular heart disease syndrome” or new association?

Polyvalvular heart disease has been reported in a handful of “private” syndromes that have been recently suggested to represent a single dominantly inherited condition, the polyvalvular heart disease syndrome.We report five cases in two unrelated families (one sporadic case in the first family and three siblings and their father in the second family) with the same association of polyvalvular heart disease, distinctive facial appearance, and, except the father in family 2, major joint hypermobility. Interestingly, in three of our patients (2 siblings and the sporadic case), electron microscopy revealed characteristic ultrastructural skin abnormalities with abnormal amorphous or microfibrillar deposits under the capillary basal membrane in the papillary dermis, suggestive of a connective tissue disorder, but different from Marfan syndrome or Ehlers-Danlos syndrome. Moreover, in family 2, three others sibs died in early infancy of their heart defect.Our two families and the other published cases might illustrate intrafamilial and interfamilial variability within a single condition. However, our two families disclose major joint hypermobility, normal stature, and ultrastructural skin abnormalities that were not described in the previous reports. These discrepancies let us to consider them as affected by a distinct disorder of the connective tissue.     

Pulmonary agenesis,microphthalmia, and diaphragmatic defect (PMD): New syndrome or association?

We present the prenatal diagnosis of a 22-week-gestation fetus with unilateral pulmonary agenesis, diaphragmatic hernia, microphthalmia, pulmonary vessel agenesis, and intrauterine growth retardation. The “association” of pulmonary agenesis, diaphragmatic defect, and microphthalmia was described previously in two patients but the resemblance was not noted by the authors. While each case differs slightly in some of the associated anomalies, it is evident that the mainstay of diagnosis is similar to the case presented here and that this represents a new syndrome or association. Am. J. Med. Genet. 86:6–8, 1999. © 1999 Wiley-Liss, Inc.     

Klippel-Feil anomaly with Sprengel anomaly, omovertebral bone, thumb abnormalities, and flexion-crease changes: novel association or syndrome?

We report on a family with Klippel-Feil anomaly (KF), Sprengel anomaly, omovertebral bone, thumb abnormalities, and flexion-crease abnormalities. This combination of abnormalities does not fit into Holt-Oram syndrome, Wildervanck syndrome, oculo-auriculo-vertebral (Goldenhar) anomaly, or the VATER complex. Clinical aspects of a KF classification are discussed. The state of molecular research on KF is briefly reported. We conclude that this set of anomalies is a novel combination, probably representing pleiotropy of a single Mendelian gene.     

Arthrogryposis multiplex congenita,craniofacial, and ophthalmological abnormalities and normal intelligence: A new syndrome?

We report on an 8-year-old boy with clinical manifestations suggestive of a new arthrogryposis syndrome. These included characteristic craniofacial abnormalities, cleft palate, arthrogryposis multiplex congenita, pulmonary hypoplasia, cryptorchidism, and unusual ophthalmological findings. There was no intrauterine growth retardation or decreased fetal movements. Despite the poor prognosis expected in early life, the patient presented with normal mental capability on follow-up. Family data showed that a maternal first cousin of the mother (mother's brother's son) had similar findings and died in infancy. Differential diagnosis included Pena-Shokeir syndrome or phenotype, Gordon syndrome, Marden-Walker syndrome, and the syndrome of arthrogryposis with ophthalmoplegia and retinopathy. The possibility of autosomal dominant inheritance with reduced penetrance is suggested for this apparently new syndrome. Am. J. Med. Genet. 71:401–405, 1997. © 1997 Wiley-Liss, Inc.     

Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: Lumping or splitting?

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are 2 rare but clinically well-described diseases caused by de novo heterozygous sequence variants in the KAT6B gene. Both phenotypes are characterized by significant global developmental delay/intellectual disability, hypotonia, genital abnormalities, and patellar hypoplasia/agenesis. In addition, congenital heart defects, dental abnormalities, hearing loss, and thyroid anomalies are common to both phenotypes. This broad clinical overlap led some authors to propose the concept of KAT6B spectrum disorders. On the other hand, some clinical features could help to differentiate the 2 disorders. Furthermore, it is possible to establish a genotype-phenotype correlation when considering the position of the sequence variant along the gene, supporting the notion of the 2 disorders as really distinct entities.     

Novel syndrome of cataracts, retinitis pigmentosa, late onset deafness and sperm abnormalities: a new Usher syndrome subtype with X-linked inheritance?

Tissues of the auditory, ocular and reproductive systems have some similarities in their protein families and structures. Consequently, syndromes comprising these systems are described. Hearing loss alone is a component of more than 400 known syndromes and is a common nonsyndromic congenital disorder. Here we describe a syndrome in five brothers with the distinctive presentation of late-onset progressive hearing loss, cataracts, retinitis pigmentosa, sperm motility and shape problems in a family from the Kurdish population in Iran. The clinical findings of these patients are presented in detail and compared to the classical Usher syndromes.     

Midline raphé, sternal cleft, and other midline abnormalities: a new dominant syndrome?

Sternal fusion defects are malformations that often present as an isolated finding. An association with multiple malformations has been reported, in particular with midline raphe and craniofacial hemangiomas and as part of the pentalogy of Cantrell. Most syndromic cases were sporadic with a few families reported with recurrence in sibs. We describe a mother and two daughters with midline raphe and sternal defects. Affected members also had double central incisors, congenital heart defect, neck webbing, bicornuate uterus and minor anomalies including long face with hypotelorism. None of the three affected relatives had hemangiomas. The manifestations of these patients do not fit any previously described condition, and we propose they represent a new syndrome. This family is also important as it points to a possible genetic cause for at least some cases of this disorder of the ventral midline.     

Prenatal and postnatal growth retardation, microcephaly, developmental delay, and pigmentation abnormalities: Naegeli syndrome, dyskeratosis congenita, poikiloderma Clericuzio type, or separate entity?

Naegeli(-Franceschetti-Jadassohn) syndrome and Dermatopathia Pigmentosa Reticularis are allelic disorders, both characterized by a congenital generalized reticulate hyperpigmentation, palmoplantar hyperkeratosis and other ectodermal symptoms. The disorders differ in their primary pigmentation localization and hair and dental manifestations. They resemble Dyskeratosis Congenita and Poikiloderma Clericuzio type in many of the skin changes, but especially the presence of leukoplakia and bone marrow disfunctioning in the first, and of telangiectasias, generalized hyperkeratosis of palms and soles, and nail pachyonychia in the latter are distinguishing features. Here we present two unrelated patients who have prenatal and postnatal growth retardation, microcephaly, developmental delay, generalized reticulate hyperpigmentation, hypohidrosis, absent fingertip prints, and absent palmoplantar hyperkeratosis. The patients differ in nail manifestations and hair colour. No Keratin14 mutation or genomic imbalance at CGHarray could be found in either of them. Although their phenotype overlaps with Naegeli syndrome, dermatopathia pigmentosa reticularis, dyskeratosis congenita and poikiloderma Clericuzio type, the differences in ectodermal manifestations, immunological functioning, growth pattern and cognition may indicate the presence of a separate entity.     

Constellation of congenital abnormalities in an infant: A new syndrome or tissue-specific mosaicism for trisomy 18?

A newborn infant born to consanguineous (first cousin) parents was noted to have complex congenital heart defect and minor anomalies suggestive of trisomy 18. Blood lymphocyte and skin fibroblast karyotypes were normal. He died in the neonatal period of postoperative complications. On interphase fluorescence in-situ hybridization (FISH) using autopsy specimens, a significant number of cells in the liver (17%) were trisomic for chromosome 18, compared to normal control liver tissue. However, interphase FISH analyses of blood lymphocytes, skin fibroblasts, and kidney tissue were normal. It is our opinion that this apparent mosaicism for trisomy 18 in the patient's liver may be spurious, though it brings into focus the issue of possible tissue/organ-specific mosaicism. The anomalies in this infant do not resemble a previously described malformation syndrome. Parental consanguinity raises the possibility that this represents a new autosomal recessive malformation syndrome. © 1996 Wiley-Liss, Inc.     

Cataracts,motor system disorder,short stature,learning difficulties,and skeletal abnormalities: A new syndrome?

We present a 4-generation family in which affected individuals have cataracts, a motor neuronopathy with upper motor neuron signs, short stature, developmental delay, and skeletal abnormalities. An additional symptom is weakness during pregnancy which resolves after delivery. The condition is inherited in an autosomal dominant manner. The manifestations and inheritance are not found in any previously described conditions. We consider that this is a new syndrome. © 1996 Wiley-Liss, Inc.     

Variant of Coffin-Siris syndrome or previously undescribed syndrome?

We describe a 23-year-old woman with growth and mental retardation, hypoplasia of the nails and distal phalanges, particularly of the fifth fingers and toes, hirsutism, and a “coarse” face with large mouth and large tongue, and bushy eyebrows. Follow-up from birth to adulthood showed that developmental delay and hypoplasia of nails and distal phalanges are permanent signs. Sparse scalp hair, hypotonia, and feeding difficulties were present in early infancy. Later, growth retardation, hirsutism, and a “coarse” face with midface hypoplasia, broad nose, and large mouth became more impressive. Differential diagnosis includes a number of conditions, particularly Coffin-Siris syndrome, which is the most likely but not completely convincing diagnosis. Therefore, this woman might represent a variant of Coffin-Siris syndrome or a new entity. © 1996 Wiley-Liss, Inc.     

A family with radio-ulnar synostosis, scoliosis, and thick vermilion of lips: a novel syndrome or variant of Giuffrè-Tsukahara syndrome?

We report on a three-generation Chinese family presenting with a recognizable condition consisting of radio-ulnar synostosis, short stature, scoliosis, distinctive craniofacial features (thick vermilion to the lips, prominent eyes, and flat malar region), and a shortened and thickened femur neck. The inheritance of the trait was presumably autosomal dominant. The lack of microcephaly in the family suggested a variant of Giuffè-Tsukahara syndrome but could represent variability