D. Licata

Arterial tortuosity syndrome

We describe a patient with arterial tortuosity syndrome (ATS), a rare disorder comprising generalized tortuosity and elongation of all major arteries, soft skin, joint laxity, severe keratoconus, and diffuse tortuosity of the carotids and of intracranial arteries. The patients probably affected brother and sister died at an early age. Cytochemical studies excluded Ehlers-Danlos type IV and type VII syndromes. We review 11 previously described patients.

Macrocephaly–cutis marmorata telangiectatica congenita without cutis marmorata?

We report on two patients with clinical manifestations consistent with a diagnosis of macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC). Both showed macrocephaly with high forehead, overgrowth, capillary hemangiomata involving philtrum, nose, and lips, and redundant skin. In addition, the first had cutis marmorata and joint laxity. The second had postaxial polydactyly of hands and feet, cutaneous syndactyly of third and fourth right fingers and of second and third right toes without evident cutis marmorata. A magnetic resonance imaging scan showed cerebral alterations in both patients. The first had bilateral cortical dysplasia with frontal bilateral myelinization defect of corona radiata. The second had mild intertonsillar widening, cavum septi pellucidi, small porencephalic areas in the anterolateral region of cellae, and subsequently developed a nonobstructive hydrocephalus. Reviewing all reported cases we propose a new criterion for M-CMTC diagnosis.

Bladder carcinoma in Costello syndrome : Report on a patient born to consanguineous parents and review

We report on a 12-year-old boy with Costello syndrome born to consanguineous (first cousins once removed) parents, supporting the hypothesis of recessive transmission of this syndrome. At age 11 years, the patient developed a bladder carcinoma, a rare pediatric tumor not previously described in Costello syndrome. This suggests that an increased risk of malignancy may be part of this condition.

Gershoni-Baruch syndrome: Report of a new family confirming autosomal recessive inheritance

Gershoni–Baruch syndrome is a multiple congenital malformation complex characterized by omphalocele, diaphragmatic hernia, cardiovascular abnormalities, and radial ray defects. Autosomal recessive inheritance is suggested. We describe two additional cases from a single family (sister and brother) delivered through termination at 23 and 9 weeks of gestation, respectively. The first fetus showed a spectrum of schisis defects without any limb involvement while the second bore mainly malformations of hands and feet. The occurrence of two different syndromes in the same family is highly improbable, but, considering both malformation complexes as possible manifestations of the same disease, a diagnosis of Gershoni–Baruch syndrome appears the most reasonable. These new familial cases bring further support to the hypothesis of an autosomal recessive inheritance of this syndrome.

Long first metacarpal in monozygotic twins with probable Baller-Gerold syndrome

We report on a pair of monozygotic twins with probable Baller-Gerold syndrome (BGS). Twin A had severe coronal craniosynostosis. Twin B had right radioulnar and ipsilateral first metacarpal hypoplasia. Both had bilateral fifth finger clinodactyly. Assuming that the twins were truly monozygotic, a single genetic disorder (i.e., BGS) could explain the variable expression. Together the twins have the typical anomalies of BGS. The diagnosis was supported by the metacarpophalangeal profile (MPP) which confirmed hypoplasia of the first right metacarpal in Twin A and bilateral fifth finger brachymesophalangy in both twins. Furthermore, the MPP showed an unexpected abnormal lengthening of the first metacarpal (unilateral in Twin A and bilateral in Twin B), a previously undetected radial ray defect in BGS. These findings suggest the possibility that the MPP may assist recognition of mild cases of BGS such as those with apparently isolated craniosynostosis or isolated upper limbs defects.

Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto‐metaphyseal dysplasia

Fronto-metaphyseal dysplasia (FMD) is an uncommon but clinically striking condition affecting bone and connective tissue. The terms used to define this syndrome fail to cover all the reported findings, the abnormalities not being confined to the metaphyses and to the frontal bones. We report on a patient who, in addition to the clinical manifestations characteristic of the syndrome, showed esophageal atresia with distal tracheoesophageal fistula. Particular emphasis is given to the extraskeletal manifestations of the syndrome reported in the literature.

Patterson-Lowry rhizomelic dysplasia: report of two new patients.

We report two new patients with the Patterson–Lowry rhizomelic dysplasia characterized by very short humeri, coxa vara with proximal femoral epiphyseal involvement, short metacarpals, metatarsals and phalanges. The expression of clinical and radiological characteristics is significantly variable, but the unique proximal metaepiphyseal appearance of humeri makes the syndrome easily identifiable. All the reported patients are sporadic. The genetics of the syndrome remain unclear for the moment.

Cerebro-reno-digital (meckel-like) syndrome with limb malformations and acetabular spurs in two sibs: A new MCA syndrome?

Meckel syndrome (MKS) is a lethal autosomal recessive malformation syndrome comprising central nervous system abnormalities (usually occipital meningoencephalocele), multicystic kidneys with fibrotic change of the liver, and polydactyly (postaxial in most cases). Additional anomalies (microphthalmia, cleft palate, ear defects, cardiac, intestinal, and genital anomalies) are frequent. Short limbs [Malguria et al., 1996], and short bowed limbs have also been reported [Majewski et al., 1983], but a true bone dysplasia has never been observed [Saalonen and Paavola, 1998]. Recently, we observed two brothers with a condition suggestive of MKS but with additional short incurved long distal bones and acetabular spurs. Patient 1 was the first conceptus of healthy Caucasian nonconsanguineous 28-year-old mother and 33-year-old father. Routine ultrasound study at 15 weeks of gestational age showed a fetus with posterior encephalocele, multicystic kidneys, and short, malformed limbs. Amniocentesis showed a 46,XY karyotype. Examination at 16weeks showed amacerated fetus with apparent female external genitalia. The crown-rump length was cm 10 (50–75th centile) and foot length 1.8 cm. The fetus had an occipital encephalocele and posterior cervical rachischisis, protuberant abdomen, bilateral polycystic kidneys, and hepatic cystic dysplasia. No anatomical reference about the internal sex organswas reported. Postaxial hexadactyly of hands and feet, anterior bowing of tibiae and bilateral club foot were present. The radiographic examination (Fig. 1) showed evident cranio-rachischisis, 11, somewhat short and horizontal pairs of ribs, slightly bowed humeri, radii and ulnae, slightly curved femora and very short, angulated tibiae and fibulae. Five calcifiedmetacarpals and six digits were present on hands and feet. The iliac boneswere short in their vertical dimensionwith round lateral borders. The lowermargins of the ilia had trident shape and medial spurs. A tentative diagnosis ofMeckel orMeckel-like syndromewas made and the parents were counseled about a 25% recurrence risk. Patient 2: 6 months later themother came to the hospital for a routine echographic control of her second pregnancy at 9 weeks of gestational age. The ultrasound study showed a fetus with a malformation complex similar to that observed in the previous fetus. TheCRLwasmm23.7 (þ2 SD). Therewas a large posterior encephalocele, bilateral polycystic kidneys, hepatic cystic dysplasia, and short malformed lower limbs. Examination was possible only on small parts of the fetus (part of the thorax, one upper limb, both lower limbs, pelvis, and one gonad) at 10 weeks. Postaxial heptadactyly of the only hand, postaxial hexadactyly of both feet, anterior bowing of tibiae and club feet were evident (Fig. 2). Radiographic examination of these segments showed a slightly bowed humerus, moderately bent radius and ulna (Fig. 3); slightly curved femora and very short and angulated tibiae and fibulae. Six calcified metatarsals were evident in the right foot and apparently four in the left (Fig. 4). The iliac bones were preserved; they were short in their vertical dimension with round lateral borders. The lowermargins of the ilia had a clear trident shape with medial spurs (Fig. 5). Histopathological examination of the tibiae showed extremely bent diaphyses with irregular disposition of trabecular bone. At the apex of the bent there was accumulation of a cartilage-like substance. At the chondro–osseous junction disordered chondrocyte columns and irregularities of trabecular bone were evident. The gonad showed an ovarian type differentiation with absence of tubular structures and presence of oogonial cells. The karyotype was 46,XY.

Tetralogy of fallot in a patient with developmental coxa vara/spondylometaphyseal dysplasia‐corner fracture type (DCV/SMD‐CF) expanding the variability

Developmental coxa vara with spondylometaphyseal dysplasia-corner fracture type (DCV/SMD-CF) (Suttcliffe type of SMD) [OMIM184255] is a rare skeletal disorder characterized by short stature, short long bones, coxa vara associated with a distinctive triangular bone fragment at the infero-medial corner of the femoral neck, fragments in the lateral metaphyseal ends of some long bones, and changes in the vertebral bodieswhichappear short, tall, andovoid. Thedisorderusually becomes apparent after the children start walking. This syndrome was first described by Suttcliffe [1966] and has been subsequently reported by Cooper and Ponseti [1973], Felman et al. [1974], Kozlowski and Bellmore [1989], Langer et al. [1990], Kozlowski et al. [1992, 1993], and Lachman [1966]. A review of 18 cases, including three personal observations, has been reported by Currarino et al. [2000]. In the present letter, we describe a new patient affected by DCV/SMD-CF who in addition presented at birth with an apparently isolated tetralogy of Fallot. The patient was a preterm baby born to healthy nonconsanguineousparents.Themother (tertipara)was30and the father was 40 years old at the time of conception. A Cesarean section was performed at 33 weeks of gestation because of the appearance of toxemia. The last fetal echography showed apparently isolated short femurs. Birth weight was 1,560 g (25th centile), length 40 cm (10th centile), and head circumference 32 cm (75th centile). An echocardiograph performed at 1month of age following the appearance of a heartmurmur led to a diagnosis of Fallot tetralogy, which was surgically corrected at the age of 6 months. The psychomotor development was within normal limits. At the age of 3 years, an increasing left genu valgum was noted. A radiograph of the knee led to a diagnosis of osteochondrodysplasia. The girl was 31⁄2 years of age at the time of our first genetic evaluation.Weight was 11 kg ( 3 SD), height 82.5 cm ( 4 SD), and OFC 49.5 cm (25–50th centile), arm span 64.5 cm, U/L segment ratio 1.98. (NV for age1⁄4 1.275), hand length 10.2 cm (3rd centile), foot length 14.4 cm (3rd–10th centile). Craniofacial features were normal. The limbs appeared short [upper limb length 35.5 cm ( 4 SD), lower limb length 42.25 cm ( 4 SD)]. There were evident lumbar hyperlordosis, mild left genu valgum, mild lower limb asymmetry, and bilateral pes planus (Fig. 1). A total body radiograph showed diffuse irregular metaphyseal ends more evident in the distal radii (Fig. 2), in the proximal (Fig. 3), and distal tibiae. Irregular patchy metaphyseal sclerosis was also particularly evident. Small corner fractures were present in the lateral aspect of right and left distal radial metaphyses, in the medial aspect of right and left proximal and right distal tibial metaphyses and in the lateral distal metaphysis of the left fibula. The pelvis showed bilateral severe coxa vara, very short femoral necks with a vertical radiolucent gap and a triangular bone fragment in the inferior medial aspect of the right femoral neck (Fig. 4). The acetabular roofs and iliac bones were normal. A lateral roentgenogram of the dorso-lumbar spine revealed an ovoid shape of the vertebral bodies with anterior wedging in T11, T12, and marked hypoplasia of L1 (Fig. 5). The metacarpophalangeal profile (MPP) showed only a relative shortness of the distal phalanges. The other Z-score valueswere on average above the ‘‘zero line’’ (see the online Fig. 6 at http://www. interscience.wiley.com/jpages/1552-4825/suppmat/index.html). The Sutcliff type of SMD is an uncommon skeletal disorder easily distinguishable from other types of SMDs. An excellent review has been proposed by Currarino et al. [2000]. According to these authors, the main characteristics of this unique chondrodysplasia are: DCV, a radiograph finding not present in the first year of life, generally noted between 1.5 and 2 years