Goldberg–Shprintzen syndrome: Hirschsprung disease, hypotonia, and ptosis in sibs

Abstract

We describe a brother and sister with Hirschsprung disease, hypotonia, and ptosis. Their condition resembles that in 2 sibs reported by Goldberg and Shprintzen. We conclude that the clinical characteristics in 8 reported cases with similar clinical manifestations represent a distinct autosomal recessive syndrome, Goldberg-Shprintzen syndrome.

Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B

“…Goldberg and Shprintzen first described a HSCR/microcephaly syndrome in a pair of siblings of consanguineous parents, suggesting autosomal recessive inheritance. Subsequent case reports of similar patients with sibling recurrence or consanguinity supported this suggestion [Goldberg and Shprintzen, 1981;Yomo et al, 1991;Fryer, 1998;Brooks et al, 1999]. In 1998, we reported six sporadic patients with microcephaly, mental retardation, and similar dysmorphism, þ/ÀHSCR, one of whom had a cytogenetically visible deletion at 2q22-23 [Mowat et al, 1998].…”

“…There is considerable overlap with GSS. We think that the facies of the siblings described by Goldberg and Shprintzen [1981], Yomo et al [1991], and Fryer [1998], and the siblings and cousins from the consanguineous families described by Hurst et al [1988] and Brooks et al [1999] resemble each other strongly, that the sibling recurrence and consanguinity is relevant, and that they probably have a different condition to that we describe. They have a subtly different facial dysmorphism: the eyebrows are more arched and narrow, extending into a prominent nasal root, ptosis is more common, and the eyelashes are long and curled.…”

Intersitial deletion of 20p: New candidate region for Hirschsprung disease and autism?

“…Mutations in the adenylosuccinate lyase gene on chromosome 22q13.1-q13.2 have been reported in three sibs with autism [Stone et al, 1992], but not in a follow-up study of 119 patients with autism [Fon et al, 1993]. Finally, the appearance of autism in a small number of patients with various other genetic disorders (Fragile X syndrome, Rett syndrome, Goldberg-Shprintzen syndrome, Asperger syndrome, Brachmann-deLange syndrome, hypomelanosis of Ito, Joubert syndrome, neurofibromatosis, phenylketonuria, and tuberous sclerosis) is consistent with a genetic cause for autism and the potential involvement of a large number of genes in the development of language and social skills [Akefeldt and Gillberg, 1991;Annerén et al, 1995;Bay et al, 1993;Brown et al, 1986;Cohen et al, 1991;Folstein and Piven, 1991;Gillberg and Coleman, 1996;Holroyd et al, 1991;Hunt and Shepherd, 1993;Li et al, 1993;McKusick, 1994;Yomo et al, 1991]. This contention is further supported by sporadic reports describing a number of chromosome abnormalities, each of which has been seen in only one or a small number of patients with autism (Table I).…”

KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome

“…Interestingly, homozygous mutations of KBP, also known as KIAA1279, cause a rare but severe neurological disorder, GoldbergShprintzen syndrome (GSS), in humans (Brooks et al, 2005). GSS is characterized primarily by neurological symptoms, including mental retardation and disruption to white matter tracts (Fryer, 1998;Goldberg and Shprintzen, 1981;Murphy et al, 2006;Silengo et al, 2003;Tanaka et al, 1993;Yomo et al, 1991). Very little is known about the cellular basis of GSS and in the absence of an animal model that disrupts KBP activity, elucidation of its function during neural development and disease has remained limited.…”