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We report on a case of apparent germline mosaicism in a family of two sisters carrying a novel 19p13.13 deletion. The 11-year-old proposita was referred for evaluation of macrocephaly, moderate intellectual disability (ID), and episodic ataxia. Array comparative genomic hybridization (CGH) detected a 399 kb microdeletion with breakpoints within genes NFIX and CACNA1A. A similar deletion was also seen in the elder sibling who presented with macrocephaly, ID, and strabismus. The deletions were confirmed to be de novo after the parental aCGH analysis suggesting that this is an example of germinal mosaicism. This study contributes additional information for the newly identified 19p13 deletion syndrome and clarifies the clinical roles of genes in the involved region. This case of apparent germline mosaicism represents the only known family in the cohort of 1,800 patients analyzed by our group.

To provide data about the frequency of prenatal misdiagnosis in achondroplasia (Ach), we retrospectively abstracted data from 37 consecutive referrals of infants with Ach where ultrasound was performed prenatally. Nine of 37 (24 per cent) had a positive family history of Ach; all nine were correctly diagnosed prenatally. Of the 28 with no family history of Ach, 16 (57 per cent) were recognized to have abnormalities on ultrasound but none was given a definite diagnosis of Ach. Five families received an appropriate diagnosis of ‘most likely’ Ach and four others were given a non‐specific (but appropriate) diagnosis of some dwarfing disorder, not otherwise specified. In seven instances (25 per cent), an incorrect diagnosis of a lethal or very severe disorder was provided. These results illustrate the difficulty of making a specific prenatal diagnosis of Ach. In the face of the resulting uncertainty, physicians appear to elect to emphasize the most severe of alternative diagnoses. Given the homogeneity of mutations within the fibroblast growth factor receptor 3 (FGFR3) gene in the vast majority of patients with Ach, FGFR3 mutational analysis can be offered in every instance where a short‐limb disorder is ultrasonographically detected in the latter stages of pregnancy. This would reduce the amount of incorrect and potentially harmful information provided to families.

Transient kyphotic deformity arises in most infants with achondroplasia. In a minority, a fixed and angular kyphosis develops, which can cause serious neurologic sequelae later in life. We assessed a protocol for preventing development of such fixed kyphosis in a sequential, unselected series of 66 infants with achondroplasia. This study demonstrates the efficacy of early prohibition of unsupported sitting and, in those in whom such prohibition proves insufficient, use of bracing. When the proposed algorithm was followed, none of the infants had development of a progressive kyphotic deformity. On this basis, it appears that the secondary risks of angular kyphosis, previously estimated to be between 10 and 15% in individuals with achondroplasia, can be completely eliminated.