Infantile lethal variant of Simpson‐Golabi‐Behmel syndrome associated with hydrops fetalis

Abstract

Simpson-Golabi Behmel syndrome (SGBS) is an X-linked disorder characterized by pre- and postnatal macrosomia, minor facial anomalies, and variable visceral, skeletal, and neurological abnormalities. Since its first description by Simpson et al. [1975: BD:OA XI(2):18-24], a wide clinical range of cases has been reported. There is great variability in severity, ranging from a mild form associated with long-term survival to an early lethal form with multiple congenital anomalies and severe mental retardation. In 8 reported families, affected individuals died in infancy. Here we present 4 maternally related, male cousins with a severe variant of SGBS. One of these males was aborted therapeutically at 19 weeks of gestation following the detection of multicystic kidneys on ultrasound. The 3 liveborn males were hydropic at birth with a combination of craniofacial anomalies including macrocephaly; apparently low-set, posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with thin upper vermilion border; prominent philtrum; high-arched or cleft palate; short neck; redundant skin; hypoplastic nails; skeletal defects involving upper and lower limbs; gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in one patient, the cardiorespiratory system was structurally normal. All patients died within the first 8 weeks of life of multiple complications including pneumonia and sepsis. Two SGBS kindreds, with moderate expression of the condition, have been mapped to Xq27. It is not known whether severe, familial cases, such as ours, are genetically distinct from and map to another locus. Final resolution of the genetic basis of the phenotypic variability in SGBS must await cloning and mutation analysis of the SGBS gene(s).

Overgrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: A newly recognized syndrome?

“…The parallel cultures of patient-derived fibroblasts that were maintained in the presence of doxycycline demonstrate normal deposition of collagen fibers (magnification Â6,000). Lin et al [1999], and Terespolsky et al [1995]. Abbreviations: AV, atrioventricular; CVS, cardiovascular; ''þ'', present; ''-'', absent; ''?…”

Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome

“…Very useful tables summarizing the clinical findings in SGBS were published by Garganta and Bodurtha [1992] and by Terespolsky et al [1995]. A condensed list of major findings is reported in Table I.…”

“…The diagnosis in Opitz's Michigan family Opitz et al, 1988] was often questioned because of the severity of the clinical presentation. Another severely affected family was recently described by Terespolsky et al [1995]. Given that X-linked inheritance is apparent in both families, future molecular studies will determine whether severe forms of SGBS are caused by allelic mutations at the same locus, or by another Xlinked gene.…”

Metastatic medulloblastoma in an adolescent with Simpson–Golabi–Behmel syndrome

“…There is a wide spectrum of phenotypic presentation in individuals with SGBS [Pilia et al, 1996]. The spectrum can range from individuals who are very mildly affected to infants who die shortly after birth [Terespolsky et al, 1995;Neri et al, 1998;Filmus, 2001].…”