Recurrence risk for sibs of children with "sporadic" achondroplasia

Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but it has not been measured. Data from 11 Canadian genetics centers provide an estimate of 1/443, or 0.02%.     

Kinder mit Skelettdysplasien des FGFR3-Mutationsspektrums

Objective

To evaluate the prevalence of anamnestic indicators for sleep-related respiratory disturbances (SRD), the polysomnographic type of SRD, the underlying pathophysiological mechanisms, and the relationship between SRD and increased mortality rate in achondroplastic children and adolescents.

Method

A systematic review of the literature was performed.

Results

A total of 16 publications from 1984 to 2009 were evaluated: 2 case reports, 8 clinical case series, 1 questionnaire study with a reference population, 5 physiological, neuroradiological and molecular genetic studies, of which 3 had a reference group. There were no population-based epidemiological studies. Several factors (midfacial hypoplasia, muscular hypotonia, narrowing of the foramen magnum) related to achondroplasia contribute to the fact that achondroplastic children and adolescents have an increased risk for SRD and chronic respiratory failure. During the first year of life, there is an increased risk for sudden death, partially due to brainstem compression. This risk is reduced by compensatory factors evolving throughout childhood, thus, leading to improvement of lung function.

Conclusions

Although the items “SRD and achondroplasia”, “prognosis of SRD”, and “pathophysiology of SRD in achondroplasia” have been evaluated and discussed in several publications since 1984, the current database is limited. The results published so far stem from relatively small case series and are distorted by selection and recall bias. Because of the high risk for SRD in achondroplastic patients, it appears sensible to perform polysomnographic sleep recordings in all these patients during early childhood.     

Homozygous achondroplasia with survival beyond infancy

Homozygous achondroplasia has been thought to be uniformly lethal in the neonatal period. We describe three children, born to achondroplastic parents, who were homozygous for this disorder but who survived beyond early infancy. Two died suddenly at 37 and 33 mo; the third survives at 29 wk. At least in some instances aggressive treatment may allow others with this condition to survive with a reasonable quality of life.     

Improvement in ventriculomegaly following cervicomedullary decompressive surgery in children with achondroplasia and foramen magnum stenosis

The role of cervicomedullary decompression (CMD) in the care of hydrocephalic achondroplastic children who present with simultaneous foramen magnum stenosis is not well understood. We sought to determine the percentage of symptomatic achondroplastic children with foramen magnum stenosis who had stabilization or improvement in ventriculomegaly following CMD. The authors retrospectively reviewed the records of pediatric patients at Cedars‐Sinai Medical Center with achondroplasia and signs of progressive ventriculomegaly who underwent CMD for symptomatic foramen magnum stenosis between the years 2000 and 2018. Clinical outcomes included changes in fontanelle characteristics, head circumference (HC) percentile, and incidence of ventriculoperitoneal (VP) shunting. Radiographic outcomes measured included changes in Evans ratio. We excluded individuals who were shunted before CMD from our study. Sixteen children presented with symptomatic foramen magnum stenosis and full anterior fontanelle or jump in the HC percentiles. Two children underwent placement of a VP shunt before decompressive surgery and were excluded from further analysis. Of the remaining 14 children who underwent CMD, 13 (93%) showed softening or flattening of their fontanelles post‐operatively. Ten of these 14 children had both pre‐ and post‐operative HC percentile records available, with 8 showing increasing HC percentiles before surgery. Seven of those eight children (88%) showed a deceleration or stabilization of HC growth velocity following decompression of the foramen magnum. Among 10 children with available pre‐ and post‐operative brain imaging, ventricular size improved in 5 (50%), stabilized in 2 (20%), and slightly increased in 3 (30%) children after decompression. Two children (14%) required a shunt despite decompression of the foramen magnum. A significant proportion of children with concomitant signs of raised intracranial pressure or findings of progressive ventriculomegaly and foramen magnum stenosis may have improvement or stabilization of these findings following CMD. CMD may decrease the need for VP shunting and its associated complications in the select group of hydrocephalic children with achondroplasia presenting with symptomatic foramen magnum stenosis.     

Recurrence risk for sibs of children with “sporadic” achondroplasia

Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but it has not been measured. Data from 11 Canadian genetics centers provide an estimate of 1/443, or 0.02%. Am. J. Med. Genet. 90:250–251, 2000. © 2000 Wiley‐Liss, Inc.     

AN AUTOPSY CASE OF ACHONDROPLASIA IN ONE OF BINOVULAR TWINS OF DIFFERENT SEX

An achondroplastic female newborn in one of binovular twins of different sexw as reported. The incidences of this peculiar dwarfism were also reported, which were based on the delivery records in our clinic for the recent 5 years and on the statistics of over 90,000 autopsy cases in Japan from 1958 to 1964.
Neither apparent hereditary factor nor contributory clinical history of their parents was detected. The autopsy of the twins revealed that the female infant was a typical achondroplastic dwarf associated with pulmonary hypoplasia and hypoplasia of the endocrine organs, and that the male infant was a nonachondroplastic premature baby of 8 months gestation, who died of respiratory distress due to hyaline-like membrane.
Histochemical findings of the ground substance of the cartilages, fixed by different fixatives, of both cases were compared. After formalin fixation, in the abnormal cartilages of the achondroplastic acid mucopolysaccharide diminished distinctly. After ethanol fixation, however, much of the acid mucopolysaccharide was retained. The histochemical tests suggested that the intense reactions in the ethanol-fixed materials would be due to the presence of chondroitin sulphuric acid A or C. Therefore, chondroitin sulphuric acid in the achondroplastic cartilage might not be bound with protein of the ground substance.     

Confidence bands for the growth of head circumference in achondroplastic children during the first year of life

Confidence bands are established for the growth of head circumference in achondroplastic children during their first year of life. The model where a = (1, t,t²) and t is age expressed in months provides the best estimated propulation mean curve with 95% confidence limits.     

Computerized tomography of the foramen magnum: achondroplastic values compared to normal standards

Computerized tomographic dimensions of the foramen magnum of 63 achondroplastic individuals were compared to standards established for nonachondroplastic individuals. The size of the foramen magnum in patients with achondroplasia was small at all ages, particularly in those with serious neurologic problems. The data suggest that measurement of the foramen magnum may identify achondroplastic individuals at high risk of developing neurologic complications.     

Metacarpophalangeal relations in 21 Danish patients with achondroplasia

Hand radiographs of 21 Danish patients suffering from achondroplastic chondrodystrophia were obtained to study the metacarpophalangeal relations. Mean pattern profiles based on z-scores were made for males, females, children, and adults. Metacarpal index and relative slenderness for metacarpals and proximal phalanges were calculated. The second to fourth metacarpals and third and fourth proximal phalanges were disproportionately short, and the distal phalanges were disproportionately long. The relation between hand size and height seemed to be the same for the achondroplasts as for normal persons. The metacarpal sign was found in four of the 21 patients.     

Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents

Three achondroplastic sisters born to normal parents are reported. This report constitutes an unique example of germinal mosaicism in the human.     

Prenatal diagnosis in two pregnancies of an achondroplastic woman

We present the results of the ultrasonographic examination of two successive pregnancies of an achondroplastic woman. The limb bones were measured and shown to be normal in length. Other pertinent literature reports are discussed.     

From Horus the child to Hephaestus who limps: a romp through history

The question of why Hephaestus, the Greek god of smiths, limped has been the subject of much debate, mainly on mythological grounds. This debate extended also into the field of medical diagnosis, with attempts at defining the nature of the deformity that made the crippled Hephaestus the buffoon of the other Olympic gods. One problem encountered in these debates was the changes to which the ugly young Hephaestus was subjected with the passing of time-from a limping deformed youth to the later dignified and normal man. While some authors, largely influenced by poetic Greek texts and vase paintings, attributed the limp to talipes (club-feet), others pointed to certain features suggestive of achondroplasia. Since the image of the early Hephaestus is based mainly on the much earlier concept of the Egyptian god Ptah, who as the triune god of the resurrection sometimes is depicted as an achondroplastic dwarf (Ptah-Pataikos), the suggestion of the possible achondroplastic dwarf-like nature of the early Hephaestus is not implausible. It is supported by similarities in the image of Hephaestus to some features in other Egyptian gods, such as the domestic god Bes, the guardian of the new-born, and the Horus the Child or Harpocrates (Greek), yet another protector of youth and "the symbol of everything that is young and vigorous" [Budge, 1969: The Gods of the Egyptians, or Studies in Egyptian Mythology. Volume I.]. The characteristic feature of this child-god is the "lock of Harpocrates" on the right side of his head. That this lock can sometimes also be seen not only on the head of Ptah-Pataikos and of Bes but also on the young Hephaestus is highly suggestive of the Egyptian influence on his image. Recently, however, another interesting explanation of Hephaestus's limp has been suggested that may explain why the Egyptian influenced image of the early achondroplastic Hephaestus changed to the later, more Grecian view of the smith-god who hobbled because of club-feet. Improvements in composition-analysis of samples from antique statues and various utensils have led to the suggestion that the introduction of new smelting techniques in antique times may have exposed ancient metal workers to the effects of various toxic metals causing, for instance, chronic lead poisoning or, more relevant here, chronic arsenic poisoning causing peripheral neuritis with weakness and lameness of one or both lower extremities. Later changes in smelting technique, and recognition or guess-work of a possible connection between these techniques and toxic effects, may explain the change from the buffoon-like achondroplastic walk to the club-footed limp and eventual normal behaviour of Hephaestus, the Smith. In other words: Did Hephaestus limp because of his arsen-neuritis?     

Achondroplasia and thanatophoric dwarfism in the newborn

Out of a total of 64,000 births in St. Mary's Hospital, Manchester, 17 were originally diagnosed as having achondroplasia. When the diagnosis was reviewed, 10 of these infants proved to be thanatophoric dwarfs, 3 had inherited achondroplasia, 1 was apparently a mutant achondroplastic, while 3 others had other forms of non-achondroplastic chondrodystrophy. All 10 thanatophoric dwarfs but only one other child in the series were still-born. It is concluded that both the birth rate and the perinatal mortality rate for achondroplasia are much lower than was previously believed.
The clinical features of 10 infants with thanatophoric dwarfism in this series are reviewed and a high incidence of associated defects noted. There was an excess of affected males and one pair of affected sibs occurred suggesting autosomal recessive inheritance, with sex-limitation or early loss of female embryos, in thanatophoric dwarfism.
The implications of this diagnostic heterogeneity are important in counselling parents of apparently achondroplastic infants.
The necessity for postulating a high mutation rate to the achondroplasia gene depended upon the assumption that about 80% of such infants died. The results reported here have suggested that most of this mortality is accounted for by thanatophoric dwarfs and consequently it is no longer necessary to postulate a mutation rate greater than 1:100,000 at most in achondroplasia.     

Growth of the foramen magnum in achondroplasia

Foramen magnum growth curves in achondroplasia and in the general population are presented. The achondroplastic foramen magnum is small at birth, and during the first year it has a severely impaired rate of growth especially in the transverse dimension. This markedly diminished growth results not only from abnormal endochondral bone growth but also because of abnormal placement and premature fusion of the synchondroses. Evaluation of the foramen magnum in achondroplasia should address absolute size of the transverse and sagittal dimensions, shape, and growth centers to determine growth potential of this area.     

Patellofemoral disorders presenting as bilateral locked knees in achondroplasia

Patellofemoral disorders in achondroplasia, to our knowledge, have not been reported in the literature. We describe an unusual case of bilateral locked knees in an achondroplastic patient secondary to intra-articular subluxating patellae and symmetrical chondral flap lesions of the femoral trochlea which were treated by arthroscopic resection. We suggest that abnormal kinematics may cause patellofemoral complications in achondroplasia.     

Patient with double heterozygosity for achondroplasia and pseudoachondroplasia,with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia,Fairbank type

We present a 7½-year-old girl with achondroplasia and pseudoachondroplasia. Her mother has achondroplasia and her father has pseudoachondroplasia. Radiographic manifestations of these two conditions from infancy to age 6 years are outlined. The findings in this patient are compared with those of achondroplastic patients and pseudoachondroplastic patients of similar ages. Our review of radiographs of many pseudoachondroplastic patients and subsequently of those of patients with multiple epiphyseal dysplasia (MED), Fairbank type, reinforced our opinion that pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type, are closely related conditions. MED, Fairbank type, may be the mildest form of pseudoachondroplasia. Recently published electron microscopic findings also suggest this. © 1993 Wiley-Liss, Inc.     

Prenatal sonographic diagnosis of hypochondroplasia in a high-risk fetus

Hypochondroplasia (HCH) is caused by mutations in the fibroblast growth factor receptor type 3 (FGFR 3). Prenatal diagnosis of HCH based exclusively on the sonographic measurements of the fetal skeleton is difficult and has not been reported. We describe a newborn infant with HCH who was born to a mother with achondroplasia (ACH) and a father with HCH. Serial sonographic measurements were recorded from 16 weeks of gestation. All measurements remained normal up to 22 weeks of gestation. At 25 weeks of gestation, the long bones began to appear shorter than expected for gestational age, while the head measurements (biparietal diameter and head circumference) remained normal. The measurements were sufficiently different to distinguish from findings in normal and achondroplastic fetuses. Our findings suggest that it is possible to distinguish the normal fetus from a fetus affected with HCH and to distinguish HCH and ACH from each other based on the sonographic measurements alone. To our knowledge, this is the first report of longitudinal sonographic measurements of HCH in the second and third trimesters.     

Adoption as a natural experiment

Adoption provides a unique opportunity for the study of child development. Because adopted children are raised in families in which they have no genetic relationship with their parents, and possibly none with their siblings, they provide a rare opportunity to study the relative importance of genetic, shared environmental, and nonshared environmental influences on the development of child characteristics and behaviors. Because children are adopted from a variety of circumstances and at a wide range of ages, studies of adopted children and their families provide researchers the opportunity to examine the short- and long-term influences of a wide range of environments on children's development. Because children are adopted into homes with a range of characteristics (e.g., multiracial homes), adoption provides the opportunity to study the range of influences of these homes on child development. Adoption research that focuses on each of these areas is reviewed in this article. We present conclusions about the value of adoption in psychological research and some reasons why many psychologists ignore the opportunities presented by studying adoptive families, as well as potential useful directions for future research with adopted children and their families.     

A review of personality factors in parents of gifted children and their families: Implications for research

The relationship between personality traits of parents of gifted children and their families to perceived personality development and adjustment was reviewed. Little research has been conducted on personality traits of the parents of the gifted and how these may relate to the personality development of the children themselves. An issue still left unanswered in the recent research is the origin of the unique personality characteristics of gifted children. Are these children learning these characteristics from the parents' approach to child rearing, or are they genetically endowed? More research is necessary to draw definite conclusions.