Urofacial (Ochoa) syndrome

Between 1965 and 1986 we saw 36 children with enuresis and urinary tract infection in association with “inversion” of facial expression when laughing. Urologic work-up of these patients disclosed characteristic findings of mild neuropathic bladder in all cases, with severe urinary tract damage in most of them. The clear association of distortion in facial expression and neuropathic bladder with resultant damage to the genitourinary tract should prompt urological evaluation of individuals with “inversion” of facial expression. About two thirds of the patients also had moderate to severe constipation. We suggest the term urofacial syndrome for this disorder. The occurrence of the disorder in multiple sibs, normal parents, increased parental consanguinity, and equal sex ratio indicate autosomal recessive inheritance.     

New syndrome?: MCA/MR syndrome with multiple circumferential skin creases

We describe a combination of multiple congenital anomalies, severe psychomotor retardation and symmetrical circumferential skin creases of arms and legs in a 4.5-year-old male. Craniofacial anomalies included: a high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, severe optic nerve hypoplasia, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals and posteriorly angulated ears. Head circumference was on the 10th centile and a CT scan showed dilated lateral ventricles. Intracranial pressure was not increased. Other abnormalities included: short stature, loose skin, hypotonia, pectus excavatum, inguinal and umbilical hernias, severe scoliosis, hypoplastic scrotum, long fingers and overlapping toes. Echocardiography showed tricuspid regurgitation. Chromosomes were apparently normal. Differentiation from “Michelin tire baby syndrome” and amniotic band sequence is discussed. © 1996 Wiley-Liss, Inc.     

Double or bifid zygomaticus major muscle: Anatomy,incidence, and clinical correlation

The anatomy of the double or bifid zygomaticus major muscle is investigated in a series of 50 hemifacial cadaver dissections. The double zygomaticus major muscle represents an anatomical variation of this muscle of facial expression. This bifid muscle originates as a single structure from the zygomatic bone. As it travels anteriorly, it then divides at the sub-zygomatic hollow into superior and inferior muscle bundles. The superior bundle inserts at the usual position above the corner of the mouth. The inferior bundle inserts into the modiolus below the corner of the mouth. The incidence of the double zygomaticus major muscle was 34% in the present study, as it was found to be present in 17 of 50 cadaver dissections. This study shows that variation in the individual morphology of the mimetic muscles can be a common finding. Clinically, the double or bifid zygomaticus major muscle may explain the formation of cheek “dimples.” The inferior bundle was observed in several specimens to have a dermal attachment along its mid-portion, which tethers the overlying skin. When an individual with this anatomy smiles, traction on the skin may create a dimple due to this dermal tethering effect. Clin. Anat. 11:310–313, 1998. © 1998 Wiley-Liss, Inc.     

Hypopituitarism and septooptic “dysplasia” in first cousins

Although familial forms of hypopituitarism are known, to our knowledge familial septooptic “dysplasia” in association with hypopituitarism has not been reported. We describe two first cousins with panhypopituitarism, one of whom had septooptic dysplasia. We discuss the possibility that septooptic dysplasia-hypopituitarism may be inherited as an autosomal dominant, or recessive, or multifactorial trait.     

Prenatal exposure to phenytoin,facial development,and a possible role for vitamin K

Ten patients with maxillonasal hypoplasia (Binder “syndrome”), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnacies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time. © 1995 Wiley-Liss, Inc.     

Morphology of the Nasal Apparatus in Pygmy (Kogia Breviceps) and Dwarf (K. Sima) Sperm Whales

Odontocete echolocation clicks are generated by pneumatically driven phonic lips within the nasal passage, and propagated through specialized structures within the forehead. This study investigated the highly derived echolocation structures of the pygmy (Kogia breviceps) and dwarf (K. sima) sperm whales through careful dissections (N = 18 K. breviceps, 6 K. sima) and histological examinations (N = 5 K. breviceps). This study is the first to show that the entire kogiid sound production and transmission pathway is acted upon by complex facial muscles (likely derivations of the m. maxillonasolabialis). Muscles appear capable of tensing and separating the solitary pair of phonic lips, which would control echolocation click frequencies. The phonic lips are enveloped by the “vocal cap,” a morphologically complex, connective tissue structure unique to kogiids. Extensive facial muscles appear to control the position of this structure and its spatial relationship to the phonic lips. The vocal cap's numerous air crypts suggest that it may reflect sounds. Muscles encircling the connective tissue case that surrounds the spermaceti organ may change its shape and/or internal pressure. These actions may influence the acoustic energy transmitted from the phonic lips, through this lipid body, to the melon. Facial and rostral muscles act upon the length of the melon, suggesting that the sound “beam” can be focused as it travels through the melon and into the environment. This study suggests that the kogiid echolocation system is highly tunable. Future acoustic studies are required to test these hypotheses and gain further insight into the kogiid echolocation system. Anat Rec, 298:1301–1326, 2015. © 2015 Wiley Periodicals, Inc.     

Cardio-facio-cutaneous (CFC) syndrome: Report of an adult without mental retardation

We report on a 25-year-old woman with typical manifestations of the cardio-facio-cutaneous (CFC) syndrome, but without mental retardation. She had valvular and infundibular pulmonic stenosis, brittle and woolly hair with patchy alopecia, scant body hair, dry and hypohydrotic skin, and characteristic facial traits. To our knowledge, this is the first case of CFC syndrome without mental retardation but typical cutaneous findings. © 1996 Wiley-Liss, Inc.     

Bloom syndrome does not always present with sun-sensitive facial erythema

Bloom syndrome is an autosomal recessive condition characterized by severe pre- and postnatal growth deficiency, immunodeficiency, an increased risk for malignancies, craniofacial dysmorphisms, and “typical” erythematous sun-sensitive skin lesions of the face. This facial rash has a butterfly-shaped distribution around the nose and is usually observed for the first time during the early years of life. Though reported as being a main feature of Bloom syndrome, there seems to be phenotypic variability regarding this facial skin rash among patients. It has been previously reported that in some individuals with Bloom syndrome these sun-sensitive lesions are less prominent or even absent. In this report we describe a 36 year old woman with short stature, microcephaly, several dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months after her consultation at the department of Clinical Genetics. Whole Exome Sequencing demonstrated that she had Bloom syndrome caused by a compound heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome does not always present with erythematous sun-sensitive skin lesions of the face. We would like to underline that phenotypic variation regarding this “hallmark” feature of Bloom syndrome exists. Being aware of this might prevent a delay in diagnosing this rare short-stature syndrome and, subsequently, its potential clinical implications.     

Constriction bands and limb reduction defects in two newborns with fetal ultrasound evidence for vascular disruption

Most structural anomalies attributed to vascular disruption have been inferred, though not proven, to be the result of disruptive events in utero. We report on 2 pregnancies with ultrasound evidence of disruptive events resulting in terminal limb “reduction” defects with constriction bands and other anomalies. In the first patient a fetal ultrasound study at 12 weeks post-LMP demonstrated a monochorionic (MC) twin pregnancy with a nonviable co-twin and no evidence of amniotic bands. At birth, there was a left cleft lip and palate, and terminal limb “reduction” defects with ring constrictions of the left hand and both feet. In the second patient, a routine fetal ultrasound study at 18 weeks post-LMP identified a subhepatic cyst which subsequently resolved. Fetal ultrasound examination and neonatal computed tomography (CT) scan of the liver were consistent with a hepatic infarct due to emboli from the umbilical vein. At birth, patient 2 had acrosyndactyly of the left hand with ring constrictions of the digits and reduction of the left big toe. There was no evidence of abnormal amnion. Postnatal development has been normal in both cases. We present ultrasound evidence supporting the hypothesis that vascular disruption from death of a co-twin or from in utero embolic infarcts can cause: (1) terminal limb “reduction” defects and possibly cleft lip and palate; and (2) ring constrictions similar to those of “amniotic band disruption sequence” in the absence of an abnormal amnion. Serial pregnancy ultrasound studies are recommended for evaluation of the development of fetal structural anomalies following ultrasound evidence of a disruptive event in utero. © 1992 Wiley-Liss, Inc.     

Cardio-Facio-cutaneous (CFC) syndrome: Report of two patients without hyperkeratotic skin lesions

We report on two boys with the cardio-facio-cutaneous (CFC) syndrome, but without hyperkeratotic skin involvement. They showed most of the manifestations of the CFC syndrome: growth and developmental retardation, relative macrocephaly, distinct facial appearance, sparse hair, and heart defects. Their skin was not hyperkeratotic, but patient 1 had mild atopic dermatitis and keloid-like depigmented spots.     

The neurofaciodigitorenal (NFDR) syndrome

We describe in two brothers a previously apparently unreported multiple congenital anomalies/mental retardation (MCA/MR) syndrome of high, prominent forehead, vertical groove on tip of nose, “cowlick,” ear anomalies, acrorenal field defect (incipient unilateral triphalangism, broad halluces, with unilateral renal agenesis in one of the boys), megalencephaly associated with congenital hypotonia, severe mental retardation and highly abnormal EEG without seizures, intrauterine growth retardation and primordial shortness of stature in one brother. This is a Group III (“provisionally private”) MCA/MR syndrome and presumed to be due to a Mendelian (either X-linked or autosomal recessive) mutation. We do not think these patients have the FG syndrome. The condition has been named the neurofaciodigitorenal (NFDR) syndrome.     

Sotos syndrome: Evolution of facial phenotype subjective and objective assessment

Sotos syndrome is characterized by pre- and post-natal growth acceleration, advanced bone age, developmental delay and a typical facial Gestalt. We have evaluated 45 individuals with Sotos syndrome who were between age 1 and 25 years, in order to better define the change in facial appearance over time. In each individual, a thorough assessment was made, serial photographs were reviewed, and a series of anthropometric craniofacial measurements was obtained. These were compared with age- and sex-matched normal standards. Both clinical and anthropometric evaluations show that the facial appearance which most clinical geneticists would regard as “classical” is established early in life. The head is large and dolichocephalic, with a rounded and prominent forehead, accentuated by frontoparietal balding. There is narrowing at the temples, fullness of the cheeks, and tapering to a pointed chin. With time, the normal process of facial change occurs, superimposed on that typical Gestalt. As the face lengthens, the dominance of the forehead diminishes and the chin achieves greater prominence. The mandible is long and narrow inferiorly, square or pointed, but prognathism is rare. In a small proportion of patients, a rounder face early in life may challenge diagnosis, but follow-up of these large newborn and older infants should allow diagnosis by early childhood. Visualisation of pattern profiles at different ages, supplemented by statistical measures of variability and similarity, support the clinical impressions outlined above. © 1996 Wiley-Liss, Inc.     

Clinical and molecular cytogenetic observations in three cases of “trisomy 12p syndrome”

Two unpublished cases with partial tandem duplication of 12p and one previously published case were studied by fluorescence in situ hybridization using 11 cosmid DNA probes from 12p. We propose that the smallest duplications of 12(p13.2pter) and 12(p13.1p13.33) produce the “trisomy 12p syndrome” which is characterized by heavy birth weight, macrocephaly, muscular hypotonia, short neck, flat face, high forehead, prominent cheeks, large philtrum, short nose with anteverted nostrils, and broad everted lower lip. From a review of the published cases we conclude that gross malformations are lacking in “pure” trisomy 12p, and mental retardation is severe in complete and moderate in partial trisomy 12p. Polydactyly and accessory nipples were found only with almost complete trisomy 12p. Abnormalities of hair growth may be related to a gene at 12p. The sub-band 12p11.21 may be critical for acrocallosal syndrome. Macrocephaly may be due to a metabolic disorder. © 1996 Wiley-Liss, Inc.     

Neuroendocrine carcinoma of the thymus: Aspiration biopsy,immunocytochemistry, and clinicopathologic correlates

We report three cases of well-differentiated neuroendocrine carcinoma originating primarily in the anterior mediastinum which had been initially investigated by fine-needle aspiration cytology in conjunction with immunocytochemistry and subsequently recognized as thymic in origin. Aspirates consisted of loosely cohesive or aggregated medium sized elements with round to oval nuclei and scanty cytoplasm. in all cases the Romanowsky stain provided an excellent delineation of definite paranuclear inclusion-like structures having a semicircular or discoid appearance which appeared to contain cytokeratin by immunocytochemical studies and were very similar to the intermediate filament paranuclear “buttons” found in neuroendocrine Merkel cell carcinoma of the skin. This appears to be a novel cytologic observation for thymic neuroendocrine carcinoma. We discuss the significance of the above cytologic and immunocytochemical findings and their possible role in the diagnosis of thymic neuroendocrine carcinoma by fine-needle aspiration biopsy. © 1995 Wiley- Liss, Inc.     

Severe axial anomalies in the oculo-auriculo-vertebral (Goldenhar) complex

We have studied 4 infants with oculo-auriculovertebral (OAV) complex or Goldenhar “syndrome” who also had severe axial anomalies, including multiple vertebral segmentation errors affecting the thoracic and the lumbar spine. One of them presented a previously unreported pattern of vertebral and rib anomalies similar to spondylocostal dysostosis. Three patients had twins, and all 4 patients had other associated non-skeletal malformations which affected the midline, i.e., cleft lip and palate, esophageal atresia with tracheoesophageal fistula, and ventricular septal defect. The broad extent of the axial anomalies, the association with midline defects and twinning, and the combination in the same patient of two distinct conditions support the concept that OAV complex is a polytopic developmental field defect arising during blastogenesis. © 1993 Wiley-Liss, Inc.     

Weaver syndrome in two Japanese children

We report on 2 Japanese patients (a 3-year-old girl and an 20-month-old boy) with the Weaver syndrome. The clinical manifestations are mild mental retardation, overgrowth with accelerated bone age, minor facial anomalies including broad forehead, mild hypertelorism, depressed nasal bridge, accentuated philtrum, micrognathia and large ears, and unique behavior characteristics with some social withdrawal. The nosology of the Weaver and Simpson–Golabi–Behmel syndromes is discussed.     

The costello syndrome: Report of a case and review of the literature

Summary A 5-year-old girl with the Costello syndrome is reported. Her clinical manifestations included growth and developmental delay, a distinct facial appearance with sparse and curly hair, nasal papillomata, and dark loose skin of the hands and feet. These manifestations, especially nasal papilloma, an age-dependent anomaly, are distinct in the Costello syndrome.     

Some clinical effects of oestrogen-progestogen therapy in surgically castrated women

This study reports some of the effects of oestrogen and progestogen therapy. Forty-nine women who had undergone hysterectomy and bilateral salpingo-oophorectomy took part in a double blind crossover study during which they received ethinyl oestradiol 50 μg/day, norgestrel 250 μg/day, the combination of these substances “Nordiol” and placebo. Somatic complaints were assessed at monthly interviews and weight and blood pressure recorded. The addition of norgestrel to ethinyl oestradiol therapy resulted in less dryness of skin but significantly increased mastalgia and breast size. There were no significant differences between drugs on amount of facial hair, acne, arthralgia, pruritus vulvae, vaginal discharge, vaginal odour, dyspareunia, weight or blood pressure. There was a significant reduction of diastolic blood pressure with the time duration of the study.     

The acrocallosal syndrome

We report two unrelated patients, a three-year-old girl and an 8 8/12-year-old boy with the newly described “acrocallosal” syndrome. The main manifestations of the syndrome are unusual facial appearance, pre- and postaxial polydactyly, mental retardation, and absence of the corpus callosum. Cause remains unknown.     

Small patella syndrome

We report on 2 sporadic cases of small patella syndrome (coxo-podo-patellaire syndrome) most probably representing new mutations. Both children showed retarded patellar bone age (small patellae in Patient 1 and absent patellae in Patient 2) and pelvic abnormalities. Patient 1 who was fully investigated had an unusual facies with characteristic morphological abnormalities of the forefoot and generalized bone changes. Patient 2 was not available for examination and only X-ray films of his knees, pelvis, and chest were available. These were all abnormal. He was said to have an “unusual facies” with flattened nose and prominent forehead but no further information was available. We think that small patella syndrome (coxo-podo-patellaire syndrome) is a generalized bone dysplasia with morphological and diagnostic radiographic appearances. © 1995 Wiley-Liss, Inc.