Weight for age charts for children with achondroplasia.

To develop accurate weight for age charts for individuals with achondroplasia. These novel weight for age, gender-specific growth curves for achondroplasia patients from birth through 16 years were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. Weight for age data from 301 subjects in this achondroplasia cohort, constituting 1,964 total weight measurements, are presented in these weight for age curves. Percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum by gender, using a 1 month window (+/-0.5 months) around each time point of interest. Percentiles were smoothed using a quadratic, penalized smoother by a semi-parametric model approach. Raw weight data from the achondroplasia cohort are compared to that of average stature children presented in the current CDC growth curves, divided into 0-36 months and 2-16 years. There was overlap of birth weight between achondroplasia and average stature infants. This statistical modeling method can be applied to other anthropometric parameters collected from this achondroplasia cohort (e.g., length, BMI), other skeletal dysplasia diagnoses, and to syndromic, non-skeletal dysplasia diagnoses which may benefit from standardization of weight for age.

Clinical, pathological and genetic features of women at high familial risk of breast cancer undergoing prophylactic mastectomy.

Prophylactic mastectomy (PM) is a risk-management option for women at high familial risk of breast cancer (BC). This study describes the PM experience of women enrolled in a large observational cohort study involving families with a history of hereditary breast cancer. Within 357 multiple-case BC families [119 (33%) BRCA1 or BRCA2 mutation positive], identified via family cancer clinics, 49 cases of PM [21 (43%) BRCA1 or BRCA2 mutation positive] were identified and their clinical, pathological and genetic features reviewed. Families with at least one incidence of PM displayed stronger breast/ovarian cancer histories than did families without PM. Median age at time of PM was 45 years (range 28-58). Ten cases (21%) were bilateral PMs in unaffected women and 39 cases were contralateral PMs in women with prior invasive BC (71%) or ductal carcinoma in situ (DCIS) (8%). Most (88%) underwent total mastectomy. Unnecessary axillary surgery occurred in eight subjects (16%). Malignant histology was found in three PM specimens (6%). Prior to genetic testing, PM was performed in two women who were subsequently shown not to carry the mutation specific to their family. Optimal utilization of genetic testing to guide surgical decision making, appropriate surgical technique and careful pathology examination of PM specimens, are important issues to consider prior to PM in women at high familial risk of BC.

Hypercalciuria and urolithiasis in a case of Costello syndrome.

Costello syndrome is characterized by postnatal growth deficiency, mental retardation, curly hair, coarse characteristic face, and loose skin of hands and feet. Patients with this syndrome have a high incidence of cardiac involvement, including arrhythmia, atrial septal defect, and hypertrophic cardiomyopathy. We report a 16-year-old adolescent female with Costello syndrome who presents with hypercalciuria and urolithiasis.

Involvement of the humerus in two generations with spondyloepiphyseal dysplasia.

Children with spondyloepiphyseal dysplasia present with a disproportionate short stature, platyspondyly, scoliosis, coxa vara, and clubfeet. Extraskeletal manifestations such as retinal detachment and deafness have been reported. The authors report two patients, a mother and her daughter, aged 35 and 6 years, with findings of pseudarthrosislike lesions in the middiaphysis of both humeri. The mother had minimal symptoms that resolved spontaneously, and the child had no symptoms related to these lesions. The radiographs of the mother show complete remodeling of the lesion. The pseudarthrosislike lesion of the humerus may be one of the manifestations of spondyloepiphyseal dysplasia congentia. In time, the bone remodels completely. Because this is a relatively new radiographic finding, the authors suggest performing a radiograph of the humeri in patients with spondyloepiphyseal dysplasia congenita at least once during childhood.

Medical complications of achondroplasia: a multicentre patient review.

Achondroplasia is the most prevalent chondrodysplasia and numerous authors have documented the varied social and medical complications that may compromise a full and productive life. Complications include cervicomedullary compression, spinal stenosis, restrictive and obstructive lung disease, otitis media, and tibial bowing, among others. These known complications have led to recommendations for the anticipatory management of such patients. There are relatively few data on the actual rates and timing of these problems. This paper reports data on the rates and age of occurrence of several of these complications based on a review of recorded chart information of 193 patients ascertained from several well established genetic centres with a known interest in the chondrodysplasias. The length of follow up varied and the rates of occurrence at specific age intervals were used to estimate the cumulative percentage affected for each complication. The report includes information on otitis media, ventilation tubes, hearing loss, tonsillectomy, speech problems, tibial bowing and osteotomy, ventricular shunting, apnoea, cervicomedullary decompression, and neurological signs attributable to spinal stenosis.

Lateral meningocele syndrome: three new patients and review of the literature.

One female and two male patients with multiple lateral meningoceles are presented. They do not have neurofibromatosis or Marfan syndrome and share findings with the two previously described patients with multiple lateral meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was titled "familial osteosclerosis," because osteosclerosis was present in the proposita and her mother; the patient described by Philip et al. [1995: Clin Dysmorphol 4:347-351] also had increased bone density of the skull base and the sutures. Thickened calvaria were present in one of our patients; two had a prominent metopic suture. Other shared findings include multiple lateral meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a high narrow palate, and cryptorchidism in males. In addition, our patients showed ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short umbilical cord was noted in two patients. One had a hypoplastic posterior arch of the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our patients appear to have the same syndrome as previously reported. We suggest it be called "lateral meningocele syndrome," because of this unique finding.

Extended survival in a new case of ter Haar syndrome: further delineation of the syndrome.

We present a boy followed from age 5-13 years who is the fifth reported case of ter Haar syndrome. This is a recently-named entity comprising congenital glaucoma, hypertelorism, congenital heart defects and kyphoscoliosis, skeletal dysplasia, and developmental delay. These patients were originally thought to have an autosomal-recessive form of Melnick-Needles syndrome, and were only identified as having a distinct syndrome with the report of the fourth case. Probable autosomal-recessive inheritance is based on consanguinity in 4 of 5 cases. Ocular, cardiac, and craniofacial findings distinguish ter Haar syndrome as a distinct entity. Our patient is the longest survivor at present, suggesting that there is heterogeneity in this syndrome or, alternatively, that aggressive therapy of the congenital heart defects has significant effect.

Sponastrime dysplasia: diagnostic criteria based on five new and six previously published cases.

Sponastrime dysplasia is a dwarfing autosomal recessive bone dysplasia, the diagnosis of which is based on a combination of clinical and radiological features. The radiological features are more specific than the clinical ones. We have developed diagnostic radiological criteria based on information from our five cases and from six previously published ones.

Chiari malformation and tonsillar ectopia in twin brothers and father with autosomal dominant spondylo-epiphyseal dysplasia tarda.

We describe twin brothers and father with autosomal dominant spondylo-epiphyseal dysplasia (SED) tarda. The proband presented at 17 years with nystagmus and esotropia due to a severe Chiari malformation. A milder, asymptomatic Chiari I malformation was seen in his brother and tonsillar ectopia in his father. Although these malformations have not been described in patients with SED, they are relatively common in other bony abnormalities, particularly those involving the cranio-cervical junction. The concordance of the Chiari malformations or tonsillar ectopia in all three family members with SED suggests that this association is not coincidental. It seems possible that the downward displacement of the cerebellum occurs secondary to primary osseous abnormality, rather than due to a primary disturbance of embryological development. The lack of additional brain malformations in our patients is consistent with this theory.

Extending the spectrum of distal arthrogryposis.

We describe a mother and son with multiple, non-progressive, congenital contractures, camptodactyly and absent flexion creases, expressionless face, blepharophimosis, microstomia, and short stature. Although these cases share similarities with the autosomal-recessive Schwartz-Jampel and Marden-Walker syndromes, they have a different mode of inheritance and lack myotonia, one of the most characteristic findings of the Schwartz-Jampel syndrome. Our cases most closely resemble those previously reported as distal arthrogryposis type IIb, although in our patients the proximal joints are severely affected and extraocular involvement is absent. Hearing loss is present in one and cleft palate in the other of our patients; these findings were previously described in arthrogryposis syndromes other than type IIb. We suggest extending the spectrum of distal arthrogryposis to include these manifestations, since there appears to be significantly overlap between the different syndromes.

Bilateral duplication of the primary ulnar ossification center in Ellis-van Creveld syndrome.

A patient with Ellis-van Creveld (EvC) syndrome and bilateral duplication of the primary ulnar ossification center is presented. Abnormal ossification involving secondary ossification centers of the femur and tibia as well as duplication of primary ossification centers in the carpal bones are well described in EvC. No abnormality of ulnar ossification has been noted in patients with EvC or any other skeletal dysplasia. The occurrence of bilateral duplication of ulnar ossification centers extends the clinical findings of the EvC syndrome. The gap between the ossified areas could be misinterpreted as a fracture and thus lead to a suspicion of osteogenesis imperfecta prenatally or traumatic fracture postnatally.

Sponastrime dysplasia: five new cases and review of nine previously published cases.

Sponastrime dysplasia (SD) is a dwarfing autosomal recessive short-limb bone dysplasia. The diagnosis is established by a combination of clinical and radiological findings of which the radiological are the more specific. The current diagnostic criteria are ambiguous as demonstrated by the fact that, in our opinion, three of the five patients reported since the original article do not have this condition. Comparison of our five patients and the 9 published patients has led to development of more specific diagnostic criteria. Previously undescribed complications of this condition are subglottic stenosis and tracheo-broncho-malacia, developmental coxa vara, and avascular necrosis of the capital femoral epiphyses.

Standard curves of chest circumference in achondroplasia and the relationship of chest circumference to respiratory problems.

Several pathogenetic factors, alone or in combination, may contribute to the increased frequency of respiratory complications in achondroplasia. It has been suggested that relatively small chest circumference sometimes may contribute. However, there are no published curves of chest circumference for age in achondroplasia with which to compare patients. Nor are there data relating chest circumference to overall size in achondroplasia. We present curves of chest circumference for males and females with achondroplasia from birth through age 7 years. Additional curves for chest circumference against height are also provided. Finally, we report some preliminary data regarding the possible association of chest size with respiratory signs and symptoms.

Standard weight for height curves in achondroplasia.

Standard curves developed for the general population cannot be used to assess the growth of an individual who has a condition that results in disproportionate short stature. For this reason, efforts have been made to develop growth curves specific for several of the chondrodysplasias. However, data concerning weight for height have been largely lacking, although they may be of particular importance for conditions such as achondroplasia, where there is some consensus that an increased prevalence of obesity is a particular problem. In this paper we provide standard weight for height curves for males and females with achondroplasia, and discuss the use of several indices which have been applied to the assessment of body fat in the general population.

Apparently new syndrome of congenital cataracts, sensorineural deafness, Down syndrome-like facial appearance, short stature, and mental retardation.

We describe a previously unrecognized syndrome in two unrelated patients with congenital cataracts, sensorineural deafness, distinctive facial appearance, skeletal changes, postnatal short stature, and mental retardation.

3-Year-old phenotypic female with campomelic dysplasia and bilateral gonadoblastoma.

The authors report the case of bilateral gonadoblastomas in a phenotypic female, with a 46,XY karyotype, with campomelic dysplasia. Although campomelic dysplasia with gonadal dysgenesis should be expected to contribute to an increased risk of gonadoblastoma, this is the first documented case report of campomelic dysplasia and gonadoblastoma. Phenotypic females with campomelic dysplasia should be karyotyped once the skeletal dysplasia is recognized. phenotypic females with campomelic dysplasia should undergo gonadectomy if their karyotype includes a Y chromosome or fragment.

Genetic heterogeneity in multiple epiphyseal dysplasia.

Multiple epiphyseal dysplasia (MED) comprises a group of hereditary chondrodysplasias in which there are major anatomic abnormalities of the long tubular bones. The Fairbank and Ribbing types are the most frequently cited types of MED. They are primarily defined radiographically and are autosomal dominant conditions. Recently, MED in one family was shown to map to the pericentromeric region of chromosome 19 and is probably allelic to pseudoachondroplasia. We have tested linkage with six short tandem repeat markers from chromosome 19 to autosomal dominant MED in one four-generation family and to MED in a unique family with three of seven siblings affected and with unaffected parents. Autosomal dominant MED in family 1 was linked with a maximum LOD score, at D19S212, of 3.22 at a recombination fraction (theta) of .00. Linkage to chromosome 19 was excluded with MED in the other family, under both autosomal recessive and autosomal dominant, with either reduced-penetrance or germ line-mosaicism models. Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family. COL11A1 was excluded under a recessive model. We have confirmed linkage of autosomal dominant Fairbank MED to chromosome 19 and have demonstrated that MED is genetically heterogeneous.

Genetic homogeneity of cartilage-hair hypoplasia.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by short stature and hypoplasia of the hair. Associated pleiotropic features include deficient erythrogenesis, impaired T-cell mediated immunity, Hirschsprung's disease, and an increased risk of malignancies. CHH is most prevalent among the Old Order Amish in the United States and among the Finns, but sporadic families have been described among many other populations. We have previously mapped the gene for CHH to the short arm of chromosome 9 in Finnish and Amish families. The CHH locus resides close to D9S163 within an interval of 1.5 cM flanked by D9S165 and D9S50. In order to investigate the genetic homogeneity of CHH in various populations, we studied nine families with no genealogical connections to either Amish or Finns. No recombinants were detected between the CHH gene and any of the three closest marker loci studied, suggesting that CHH in these families results from mutation(s) at the same locus as in the Amish and Finnish families.