Mental retardation, Robin sequence, and brachydactyly: further confirmation of a new syndrome

Recently we reported two sibs, brother and sister, with a new multiple congenital anomalies/mental retardation (MCA/MR) syndrome characterized by mild to moderate psychomotor delay, Robin sequence, distinctive facial appearance, and brachydactyly. We have subsequently observed a similar pattern of anomalies in two unrelated patients who also showed additional clinical findings. This new observation supports the existence of a new syndrome and expands the phenotypic spectrum of the condition.     

Fine-Lubinsky syndrome: sibling pair suggests possible autosomal recessive inheritance

In 1983, Fine and Lubinsky reported a single patient with craniofacial anomalies, hearing loss, cataracts, microstomia, CNS anomalies, and developmental delay. Since that time, three additional patients with similar findings have been described. In each case the patients was the only affected child in his or her family. Here we describe the first brother and sister sibling pair with features suggestive of Fine-Lubinsky syndrome. Features present in one or both of our patients, and the majority of previously described individuals with Fine-Lubinsky syndrome, include: craniosynostosis/abnormal calvaria, prominent frontal bones, flat facial profiles, small noses, microstomia, hearing loss, developmental delay/mental retardation, and abnormal digits. Unusual anomalies present in our patients include marked brachydactyly of fingers and toes, camptodactyly most severely affecting the second fingers, and permanence of decidual teeth. The identification of a sibling pair with Fine-Lubinsky suggests a possible autosomal recessive inheritance pattern. It is important that parents of children with Fine-Lubinsky be informed of the increased recurrence risk associated with that type of inheritance.     

Recessively inherited brachydactyly type C

We report a brother and sister, the children of unaffected consanguineous Iraqi parents, with type C brachydactyly.     

Short trunk stature,brachydactyly, and platyspondyly in three sibs: a new form of brachyolmia or a new skeletal dysplasia?

We present a 27-year-old girl with short trunk stature, generalized rectangular platyspondyly and strike precocious calcification of costal cartilage. She had also brachydactyly, small nails, strabismus and delay of menarche. Her 16-year-old sister had also short trunk stature with severe kyphoscoliosis, hearing loss, brachydactyly, platyspondyly and mild precocious calcification of costal cartilages. Their 12-year-old brother had short trunk stature, kyphoscoliosis, brachydactyly, and platyspondyly but did not show precocious calcification of costal cartilage. The patients shared the following features: short trunk stature, brachydactyly, severe rectangular platyspondyly, broad and short femoral necks and hypoplasia of the ileum. In addition, the older sister had strike precocious calcification of costal cartilage while her sister and brother had severe kyphoscoliosis. Although short trunk stature and severe rectangular platyspondyly without significant epiphyseal or metaphyseal changes were in favor of Hobaek type brachyolmia, this diagnosis was not considered, both because, there were no specific radiological findings of this syndrome, such as elongated vertebral bodies extending beyond the pedicles laterally and all of the patients had brachydactyly which was not present in Hobaek type brachyolmia. The parents were healthy and first cousins signifying autosomal recessive inheritance. We considered that the patients could be affected by a new distinct autosomal recessive type brachyolmia or a new skeletal dysplasia.     

A new syndrome of dwarfism, brachydactyly, nail dysplasia, and mental retardation in sibs

We describe a new multiple congenital anomaly/mental retardation (MCA/MR) syndrome in chromosomally normal sibs. Both had microcephaly, a "coarse" face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a "coarse" face, digital anomalies, dwarfism, and severe mental retardation. The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X-linked semidominant gene.     

Autosomal recessive syndrome of growth and mental retardation,seizures, retinal abnormalities,and osteodysplasia with similarity to the Gurrieri syndrome

We report on two sibs, brother and sister, with a multiple congenital anomaly/mental retardation syndrome consisting of severe growth and mental retardation, seizures, retinal abnormalities, osteodysplasia, brachydactyly, prognathism, and dental malocclusion. These clinical findings were present in both patients and seem to be consistent with the phenotype of the Gurrieri syndrome. The new features described in these sibs could expand the clinical spectrum of the Gurrieri syndrome and confirm the existence of this rare autosomal recessive condition. Am. J. Med. Genet. 82:84–87, 1999. © 1999 Wiley-Liss, Inc.     

Apparently new MCA/MR syndrome in sibs with cleft lip and palate and other facial, eye, heart, and intestinal anomalies.

We report on a sister and brother with severe mental retardation, bulbous tip of the nose, long columella, cleft lip and palate, heart and intestinal anomalies, and growth retardation. This appears to be a previously unreported, autosomal recessive condition, given high resolution prometaphase chromosomes are normal.     

Syndrome of mental retardation,facial anomalies,hypopituitarism, and distal arthrogryposis in sibs

A brother and a sister presented with a malformation syndrome consisting of facial anomalies, distal arthrogryposis with camp-todactyly of fingers and “hammer toes,” severe mental retardation, and hypopituitar-ism. The girl is now 6½ years old and exhibits severe mental retardation. She has abnormal secretion of growth hormone and responded to growth hormone therapy. Her brother was born with the same facial manifestations, distal contractures, and hypopituitarism. He died unexpectedly at age 3 months of no apparent cause. The occurrence of the syndrome in 2 sibs of different sex suggests auto-somal recessive inheritance.     

Apparently new MCA/MR syndrome in sibs with cleft lip and palate and other facial,eye, heart,and intestinal anomalies

We report on a sister and brother with severe mental retardation, bulbous tip of the nose, long columella, cleft lip and palate, heart and intestinal anomalies, and growth retardation. This appears to be a previously unreported, autosomal recessive condition, given high resolution prometaphase chromosomes are normal.     

An autosomal recessive syndrome of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE).

We report a brother and sister affected by a constellation of malformations, including cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). A similar association has been reported previously by Richieri-Costa and Orquizas in a male patient born to consanguineous parents. An autosomal recessive pattern of inheritance is proposed for this syndrome.     

Short stature, brachydactyly, small ears, and a pattern of minor anomalies in brother and sister born to consanguineous parents: a hitherto unreported syndrome?

A 13-year-old boy and his 28-year-old sister had short stature, obesity, and a pattern of minor anomalies including a sloping, narrow forehead; small ears; a narrow nose with prominent bridge and long septum; short upper lip; receding mandible; and short limbs with brachydactyly and clinodactyly of little fingers. The boy also had hypoplastic external genitalia and elevated FSH. Both are of normal intelligence. There is remote consanguinity of the (normal) parents. The 2 sibs probably represent a hitherto un-recognized syndrome of possibly autosomal recessive inheritance.     

Cleft lip and palate,characteristic facial appearance,malrotation of the intestine,and lethal congenital heart disease in two sibs: A new autosomal recessive condition?

A chromosomally normal brother and sister shared a lethal pattern of anomalies including bilateral cleft lip and palate, hypertelorism, flat facial profile, flat occiput, complex congenital heart defect, and malrotation of the intestine. The male was large for gestational age, while his sister was normally grown. The girl had bifid thumbs, but the boy had only minor hand anomalies. These findings are not consistent with any previously recognized syndrome and represent a new condition with probable autosomal recessive inheritance. © 1996 Wiley-Liss, Inc.     

Bilateral sensorineural deafness and hydrocephalus due to foramen of Monro obstruction in sibs: A newly described autosomal recessive disorder

We identified a Canadian-Mennonite family in which a brother and sister have hydrocephalus due to obstruction at the foramen of Monro and profound bilateral sensorineural deafness. This appears to be a unique combination of anomalies and, to our knowledge, has not been reported previously. Both parents and a brother are phenotypically normal. The parents are second cousins. Thus, on the basis of consanguinity, affected sibs of both sexes, and in the absence of evidence for intrauterine infections or other adverse perinatal events, this syndrome is likely inherited in an autosomal recessive fashion. Am. J. Med. Genet. 68:350–356, 1997. © 1997 Wiley-Liss, Inc.     

Oculotrichodysplasia (OTD): a new probably autosomal recessive condition.

A brother and sister, the offspring of first cousins, are described with retinitis pigmentosa, trichodysplasia (hypotrichosis and structural changes), dental anomalies, and onychodysplasia. This is a pure ectodermal dysplasia of the tricho-odonto-onychial subgroup, probably due to an autosomal recessive gene.     

Chromosomal instability in two siblings with gonad deficiency: case report

Non-random de novo autosomal chromosomal rearrangements have not been shown to cause exocrine or gonadal dysfunction. We report on two siblings, a brother and a sister, both with de novo chromosomal rearrangements and gonadal deficiency including premature ovarian failure. They had normal phenotypes without additional manifestations of known chromosomal breakage syndromes (except for the gonadal dysfunction) and normal alpha-fetoprotein dosage level. The association of sperm abnormalities in the brother and ovarian dysfunction in the sister suggested an increased spontaneous chromosomal instability. Since the co-occurrence of chromosomal anomalies and reproductive failures may not be coincidental, we performed repeated chromosomal analysis of peripheral blood lymphocytes prior to proposing ICSI for IVF (for the brother). In both sibs, infertility was associated with random and non-random de novo autosomal chromosomal abnormalities. We discuss the possible relationship between these unusual clinical and cytogenetic features and their potential links to ataxia-telangiectasia.     

The Pointer syndrome: A new syndrome with skeletal abnormalities,camptodactyly, facial anomalies,and feeding difficulties

We describe a brother and sister with a unique combination of skeletal findings including camptodactyly (phalangeal dislocations), facial anomalies, neonatal respiratory problems, and feeding problems due to poor suck. Metaphyseal splaying, osteopenia, endosteal bone apposition, campomelia, and multiple fractures characterize the other skeletal abnormalities. The parents are first cousins once removed and are unaffected. These cases appear to represent a previously undescribed autosomal recessive disorder. Am. J. Med. Genet. 68:225–230, 1997 © 1997 Wiley-Liss, Inc.     

Possible new autosomal recessive syndrome of partial agenesis of the corpus callosum,pontine hypoplasia,focal white matter changes,hypotonia, mental retardation,and minor anomalies

We describe a brother and sister with severe developmental delay, hypotonia, partial agenesis of the corpus callosum, pontine hypoplasia, focal white matter degenerative abnormalities, macrocrania, frontal bossing, deep-set eyes, and hypertelorism. The brother also had Duane syndrome type II and an ectopic right ureter. The coexistence of these multiple physical and brain abnormalities in a brother and sister suggests a new autosomal recessive syndrome with a slowly progressive course. Am. J. Med. Genet. 73:184–188, 1997. © 1997 Wiley-Liss, Inc.     

A syndrome of severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations in sibs

A brother and sister presented with an uncommon malformation syndrome consisting of severe midface hypoplasia, congenital heart defect, hydronephrosis, clubfeet, hypertrichosis, hypoplasia of dermal ridges, and radiographic skeletal anomalies in the skull, hands and feet. The boy died shortly after birth; the girl lived for 16 months and exhibited severe failure to thrive, epilepsy, diminished growth, and profound motor and intellectual retardation. Additional observations include postaxial hexadactyly in the girl, and mesomelic brachymelia and peculiar, narrow fingernails in the boy. The occurrence of the syndrome in two sibs of different sex suggests autosomal-recessive inheritance.     

Sibs with growth deficiency, delayed bone age, congenital hip dislocation, and iridocorneal abnormalities with glaucoma

We report on a brother and sister with short stature, delayed bone age, developmental delay, congenital hip dislocation, and iridocorneal abnormalities with onset of glaucoma at or soon after birth. Results of endocrine evaluation were normal. To our knowledge, no similar pattern of defects has been reported previously.     

Aplasia cutis congenita associated with limb,eye, and brain anomalies in sibs: A variant of the Adams-Oliver syndrome?

Aplasia cutis congenita (ACC) may occur in isolation or with other congenital malformations. Peripheral limb anomalies and ACC are major elements of the Adams-Oliver syndrome, which is usually inherited as an autosomal dominant disorder. We report on a sister and brother with ACC and brain, eye, and transverse limb anomalies. The phalanges of the hands and feet were either short or absent. The girl also had absence of right patella, was severely mentally retarded and blind with retinal nonattachment. The boy had a falciform fold in the left eye. He died at age one week and autopsy showed partial agenesis of corpus callosum. The findings in the sibs may represent a severe variant of the Adams-Oliver syndrome, or a previously unrecognized syndrome involving vascular disruption. © 1995 Wiley-Liss, Inc.