In this issue


Expectant Australian mothers overwhelmingly support newborn screening for fragile X syndrome (FXS), Christie et al (pg. 301, DOI 10.1002/ajmg.a.35752) report.

Although FXS is the one of the most common causes of inherited intellectual disability worldwide, the mean age of diagnosis is 5.5 years for children in Australia. Newborn screening for FXS can provide early diagnoses, prevent “diagnostic odysseys” for parents, allow affected children access to early interventions, and provide a venue for giving parents reproductive information, the researchers note.

To explore the feasibility of such screening in Australia and new mothers' attitudes toward it, the researchers offered FXS testing of male and female newborns, and routine newborn screening, to 2,094 new mothers in an Australian tertiary hospital. The mothers also received information about FXS, its inheritance pattern, carrier status, and associated adult-onset disorders.

In all, 94% of mothers consented to FXS testing. Of this group, 86% completed a survey about their attitudes toward it. Almost all elected to be informed of both premutation and full mutation status, with little concern about identification of carrier status or associated adult-onset disorders. Most mothers were comfortable being approached in the postnatal period and supported testing because it did not require an additional blood test. Mothers considered an early diagnosis beneficial in preparing for a child with additional needs, and for reproductive planning, the researchers report.


Children with Pierre Robin sequence (PRS) of various types show long-term developmental outcomes within the normal range, write Thouvenin et al (pg. 312, DOI 10.1002/ajmg.a.35773).

PRS is a heterogeneous congenital defect defined by retrognathism, glossoptosis, and posterior U-shaped cleft palate. PRS can occur in an isolated fashion or can be associated with Stickler syndrome, a disease affecting connective tissue.

To better determine long-term prognoses for children with PRS, the researchers conducted a longitudinal, prospective study analyzing the long-term developmental outcome of 39 children with both types of PRS. The researchers assessed children's psychomotor and cognitive levels, speech, and eating behavior at 15 months and at ages three and six, while 24 of the oldest children were interviewed at ages 11 or 12 years. The children all had severe respiratory obstruction or required at least three months of tube feeding.

Cognitive ability increased over time. By six years of age, the cognitive ability of children with PRS was normal to above normal. At age 11 to 12 years, the proportion of those who entered junior high or middle school at the usual age was similar to that of the French general population. Moreover, the children's psychomotor and cognitive level progressed over time, from the lower to the upper range of scores for the control population.


Feigenbaum et al (pg. 360, DOI 10.1002/ajmg.a.35732) report variable phenotype among Singleton-Merten syndrome patients. In 1973, the disorder was first described in two females with abnormal dentition, unique radiographic changes especially of the hands, and severe calcification and intimal weakening of the aortic arch and valve. Since then, three additional patients with similar features have been reported, and the diagnosis has been suggested for another three individuals.

Feigenbaum et al present an update of one case, and detailed clinical phenotypes of six other patients with Singleton-Merten syndrome.

These cases occurred in two families, with vertical male-to-male transmission, indicating an autosomal dominant pattern of inheritance, they write.

The researchers identify core manifestations of the syndrome as marked aortic calcification, dental dysplasia, osteopenia, and acro-osteolysis, and to a lesser extent, glaucoma, psoriasis, muscle weakness, and jointlaxity. Additional clinical characteristics described include particular facial characteristics and abnormal joint and muscle ligaments. Both glaucoma and psoriasis can be part of the phenotype, the researchers confirmed. The cause and pathogenesis of this syndrome remain unknown.

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Figure 1A. Case 1 showing camptodactyly, boutonniere deformities, long and slender fingers, and underdeveloped nails. B-D: Case 7 showing small nails (especially of second finger) and decreased mobility in metacarpophalangeal joints (fingers are flexed maximally in b). Note marked hallux formation.