Low birth-weight, microcephalic malformation syndrome in a 46,XX girl and her 46,XY sister with agonadism: Third report of the Kennerknecht syndrome or autosomal recessive Seckel-like syndrome with previously undescribed genital anomalies

Abstract

We report on two sisters, one 46,XX with normal female phenotype, the other 46,XY with ambiguous external genitalia and agonadism. Both have a low birth weight and microcephalic malformation syndrome leading to early death. The 46,XX patient also had a diaphragmatic defect. The XY sister, in addition to absence of gonads and Mùllerian and Wolffian derivatives, had severe hypoplasia of the pulmonary artery and its branches, multicystic kidneys, and pachygyria. This combination of malformations, in part, fits in the autosomal recessive condition described by Kennerknecht et al. [1993] in a 46,XX and 46,XY pair of sibs with agonadism. The craniofacial appearance of our patients is similar to that observed in the 46,XY sister with agonadism reported by Kennerknecht et al. [1995]. On the other hand, intrauterine growth retardation, microcephaly, and pachygyria are not part of the phenotype of the Kennerknecht "syndrome" and agonadism was not present in our 46,XX patient. We suggest two hypotheses to explain the abnormal phenotype in our cases. The first is that they might represent the third sibship affected by the Kennerknecht syndrome with additional anomalies. Alternatively, our two sibs might have a Seckel or a Seckel-like syndrome. The 46,XY patient would then be the first case of Seckel syndrome with sex reversal and agonadism.

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism

“…Patient 1 (P1) and Patient 2 (P2) had frequent lower respiratory tract infections, with P1 dying of respiratory failure aged 10 years as a result of chronic lung disease. Furthermore, P1 had two siblings who died in early infancy 22 . However, aside from P2 who had a persistent lymphopenia, there was no evidence of adaptive immune deficits on clinical investigation.…”

Flores hominid: New species or microcephalic dwarf?

“…Under this hypothesis, LB1 would have a short stature with microcephaly syndrome in which both body size and brain volume are far below the norms for the extant population. Various syndromes with severe intrauterine growth retardation and proportionate (at least at birth) microcephaly have been described in modern humans, including Bangstad, Bloom, Buebel, de Lange, Dubowitz, Kennerknecht, Meier-Gorlin, Okajima, and Seckel syndromes, as well as Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type 1, MOPD type 2, MOPD-Cervenka type, and MOPD-Toriello type (Toriello et al, 1986;Bangstad et al, 1989;Opitz and Holt, 1990;Meinecke et al, 1991;Lin et al, 1995;Buebel et al, 1996;Bongers et al, 2001;Silengo et al, 2001;Faivre et al, 2002;Okajima et al, 2002;Hall et al, 2004). Several of these syndromes are associated with survival to adulthood.…”

XX‐agonadism in a fetus with multiple congenital anomalies

“…A literature review of reported cases suggests that agonadism, whether occurring with an XX or XY karyotype, could be variably associated with other extragenital malformations, including neural tube defects, omphalocele, congenital heart defects, diaphragmatic defects, and upper limb reduction [Kennerknecht et al, 1993[Kennerknecht et al, , 1995[Kennerknecht et al, , 1997Ohro et al, 1998;Silengo et al, 2001]. In addition, the fetus we described and the case reported by Kennerknecht et al [1997] probably represent the severe end of the clinical spectrum.…”