Achondroplasia-hypochondroplasia complex

We report on a 14-year-old girl with the achondroplasia-hypochondroplasia complex. This patient has been reported previously [McKusick et al, 1973], and we offer an update on her condition. The patient has clinical features different from both achondroplasia and hypochondroplasia and is mentally retarded. Radiological changes, which have occurred over 14 years, are included.     

Achondroplasia–hypochondroplasia complex in a newborn infant

We describe the case of an 8-month-old girl with achondroplasia–hypochondroplasia complex. The diagnosis was suggested antenatally when obstetrical ultrasonography at 27 weeks of gestation showed short limbs, small chest, and macrocephaly. The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. Neither had had genetic counseling or molecular testing prior to the pregnancy. Antenatal ultrasound study at 29 weeks of gestation showed a large head, very short limbs, and a small chest; the findings were more severe than in achondroplasia or hypochondroplasia alone. The patient was born by cesarean section at 37 weeks of gestation and had rhizomelic shortness of limbs with excess skin creases, large head, and small chest, diagnostic of achondroplasia. Radiographs showed shortness of the long bones and flaring of the metaphyses. She had mild hypoplasia of lungs. Molecular testing showed both the G1138A and the C1620G mutations in FGFR3, confirming the diagnosis of achondroplasia–hypochondroplasia complex. At 8 months, she has disproportionate shortness of the long bones and a large head with frontal bossing and a depressed nasal bridge. Her chest remains small, and she is on home oxygen at times of respiratory stress. She has a large gibbus. She is delayed in her motor development and has significant head lag. To our knowledge, there is only one previously published report of achondroplasia–hypochondroplasia complex. Am. J. Med. Genet. 84:396–400, 1999. © 1999 Wiley-Liss, Inc.     

Molecular characterization of a complex translocation in a newborn infant

A newborn infant was referred because of low-set ears, mild downward slant of the palpebral fissues, micrognathia with higharched palate, a flat midface, small mouth, and thin upper lip with cupid bow configuration. To some extent her cry resembled that associated with cri du chat syndrome. Cytogenetic findings with G- and Q-banding alone failed to characterize precisely the complex translocations. By the chromosome in situ suppression (CISS) hybridization technique using whole chromosome specific probes, a complex 4 breakpoint rearrangement involving both arms of a single chromosome 1 with the long arms of chromosome 5 and 11 was disclosed, i.e., 46,XX, der(1),t(1;5) t(1;11) (5qter→5q31::1p31.3→1q44::11q23→11qter;5pter→5q31::1p31.3→1pter;11pter→11q23::1q44→1qter). Gene deregulation and position effect may explain the multiple anomalies in individuals with apparently balanced translocations may shed some light towards unveiling the clinical consequences associated with aberrations which are presumably balanced. © 1993 Wiley-Liss, Inc.     

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. ? 2012 Wiley Periodicals, Inc.     

Group G streptococcal pneumonia and sepsis in a newborn infant.

A case of neonatal pneumonia and sepsis caused by a group G Streptococcus is described. Clinical and microbiological aspects of group G streptococci are compared with those of group B streptococci.     

Adrenal insufficiency and hypertension in a newborn infant with Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the 7-dehydrocholesterol reductase gene, DHCR7. The diagnosis is based on the biochemical findings of elevated plasma 7-dehydrocholesterol (7DHC) levels. Adrenal insufficiency with hyponatremia has been reported in 3 patients with severe SLOS; in those cases it was thought to be caused by aldosterone deficiency because it responded to mineralocorticoid replacement. We present a fourth patient with a severe form of SLOS and adrenal insufficiency who had unexplained persistent hypertension, a combination of signs that has not been reported previously in SLOS.