New syndrome of mental retardation, Robin sequence, and brachydactyly

We report on two sibs, brother and sister, affected with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome, characterized by mild to moderate psychomotor delay, Robin sequence, peculiar facial appearance, and brachydactyly. To our knowledge, this combination of anomalies has not been reported previously. The occurrence of a similar pattern of anomalies in brother and sister suggests autosomal recessive inheritance; however, dominant transmission with reduced penetrance cannot be ruled out in our patients, since minor clinical signs, such as brachydactyly, are also present in the father.     

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.     

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.     

Short stature,brachydactyly, nail dysplasia,and mental retardation: Further observation of the Tonoki syndrome

We studied a patient with microcephaly, short stature, type B brachydactyly, nail dysplasia, skeletal anomalies, and mental retardation. The mother of the propositus has brachydactyly of thumbs and a similar physiognomy without mental retardation. This appears to be another observation of the Tonoki syndrome, a distinct autosomal dominant or X-linked clinical entity. Am. J. Med. Genet. 80:403–405, 1998. © 1998 Wiley-Liss, Inc.     

Craniotubular dysplasia with severe postnatal growth retardation,mental retardation,ectodermal dysplasia,and loose skin: Lenz-Majewski-Like syndrome

The heterogeneous group of craniotubular dysplasias is characterized by modeling errors of the craniofacial and tubular bones. Some conditions in this category cause not only skeletal abnormalities but also a variety of mesoectodermal dysplasias, as exemplified in Lenz-Majewski syndrome (MIM 151050), which comprises craniodiaphyseal dysplasia, failure to thrive, mental retardation, proximal symphalangism, enamel hypoplasia, and loose skin. We report on a boy with a hitherto unknown multisystem disorder, including skeletal changes that were regarded as a form of craniotubular dysplasia. The patient had a large head, exophthalmos, a broad nasal root, anteverted nostrils, large auricles, thick lips, micrognathia, severe postnatal growth retardation with emaciation, severe mental retardation, sparse hair growth, enamel hypoplasia, and thin, loose skin with hyperlaxity. Skeletal changes consisted of thickened calvaria, sclerosis of the skull base and facial bones, thick ribs, and metaphyseal undermodeling of the tubular bones. In addition, generalized osteopenia was evident. The present disorder overlaps phenotypically with Lenz-Majewski syndrome; nevertheless, the absence of diaphyseal hyperostosis and proximal symphalangism in the present patient was not consistent with Lenz-Majewski syndrome. Am. J. Med. Genet. 71:87–92, 1997. © 1997 Wiley-Liss, Inc.     

Fallot complex,severe mental,and growth retardation: A new autosomal recessive syndrome?

We report on the syndromic occurrence of the Fallot complex in sibs born to consanguineous Pakistani parents. Additional manifestations included minor facial anomalies, pronounced failure to thrive, and mental retardation. Expression of the syndrome varied. While one of the four patients had cardiac malformations, another sib had only non-cardiac manifestations. The clinical findings suggest a new autosomal recessive syndrome. © 1994 Wiley-Liss, Inc.     

Megalocornea and mental retardation syndrome: a new case

We report on a new case of the megalocornea mental retardation syndrome, first described by Neuh?user et al. [1975]. Our patient had mental and motor retardation, megalocorneae, short stature, congenital hypotonia, frontal bossing, micrognathia, a cafe-au-lait spot, and ear anomalies. A literature survey is provided.     

Severe lymphedema,intestinal lymphangiectasia,seizures and mild mental retardation: Further case of Hennekam syndrome with a severe phenotype

We report on an Italian patient affected by severe lymphedema of lower limbs, genitalia and face, intestinal lymphangiectasia, seizures, and moderate mental retardation. He has a flat face, flat nasal bridge, and hypertelorism. We propose that he presents with a severe form of Hennekam syndrome. © 2002 Wiley‐Liss, Inc.     

Severe lymphedema,intestinal lymphangiectasia,seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype

We report on an Italian patient affected by severe lymphedema of lower limbs, genitalia and face, intestinal lymphangiectasia, seizures, and moderate mental retardation. He has a flat face, flat nasal bridge, and hypertelorism. We propose that he presents with a severe form of Hennekam syndrome.     

Identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E: a new syndrome or variant of Fitzsimmons-Guilbert syndrome?

We report on concordantly affected female identical twins with mental retardation, dysarthria, progressive spastic paraplegia, and brachydactyly type E. The most similar condition reported is the syndrome described by Fitzsimmons and Guilbert in uniovular twins characterized by progressive spastic paraplegia, dysarthria, brachydactyly type E, and cone-shaped epiphyses. During the last 11 years a report of only one other patient with this syndrome has been published; hence, its phenotypic delineation may be only partial. Although our patients might expand the phenotypic spectrum of this syndrome, they may represent a new disorder.     

Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome

Histone deacetylase 4 (HDAC4) serves important roles in multiple human systems, including neurological, cardiac, and skeletal functions. Mutation or deletion of HDAC4 causes brachydactyly mental retardation syndrome (BDMR), a disorder that includes intellectual disability, behavioral abnormalities, autism spectrum disorder, and craniofacial and skeletal anomalies, including brachydactyly type E. We present a case of familial BDMR, including a parent with mild symptoms of the disorder and a child exhibiting a more severe phenotype. Cytogenetic testing showed a cryptic balanced translocation in the mother that resulted in a 2q37.1 monosomy and a 10q26.1 trisomy in the son. Gene expression analyses demonstrated 67% HDAC4 expression in the mother and 23% HDAC4 expression in the son relative to normal controls, lending evidence to the hypothesis that HDAC4 modulates severity of this disorder in a dosage-dependent manner.     

Haspeslagh syndrome without severe mental retardation and pterygia?

An adult female is described with mild developmental delay, typical facies, dental anomalies, arachnodactyly and camptodactyly. In many respects she resembles four other patients described earlier, but differs in not having multiple pterygia, nor severe mental retardation. We suggest that this entity should be named Haspeslagh syndrome. The differential diagnosis is discussed.     

A second case of severe mental retardation and absent nails of hallux and pollex (Temple-Baraitser syndrome)

We present a case of a male with severe mental retardation, seizure disorder, and absence/hypoplasia of the thumb and great toe nails. This combination of clinical findings has been reported only once previously. We suggest it represents a distinct syndrome. Our case has the additional finding of broad thumbs.     

A syndrome with multiple malformations, mental retardation, and ACTH deficiency

We report on a patient with severe pre- and post-natal growth retardation, moderate mental retardation, microcephaly, unusual face with marked micrognathia and cleft palate, minor skeletal abnormalities, atrioseptal defect, hypospadias, hearing loss, and secondary adrenal insufficiency due to isolated ACTH deficiency diagnosed at 7 years of age. Family history was negative. Adrenal insufficiency is an uncommon feature in multiple malformation syndromes and may thus serve as a diagnostic handle for recognizing other possible patients with a similar syndrome.     

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.     

X-linked mental retardation syndrome with characteristic "coarse" facial appearance, brachydactyly, and short stature maps to proximal Xq.

We describe a three-generation family in which X-linked mental retardation (XLMR) is associated with minor facial anomalies and brachydactyly. Two brothers and four nephews have "coarse" facial appearance, brachydactyly with widening of the distal phalanges, short stature, and moderate mental retardation. The three obligate carrier women have normal intelligence and normal physical findings. The results of linkage analysis carried out in 1988 using restriction fragment length polymorphisms (RFLPs) were suggestive of linkage to DXYS1 and DXS101 in proximal Xq (Zmax = 1.63 at straight thetamax = 0.0) [Carpenter et al., 1988: Am J Med Genet 43:A139]. The family was restudied with 16 microsatellite loci from Xp11.4 through Xq24. Linkage analysis demonstrated significant linkage to DXS1003, ALAS2, AR, DXS986, DXS990, DXS454, DXS1106, DXS1105, and DXS1220 from Xp11.3 to Xq23 (Zmax = 2.53 at straight thetamax = 0.0). Recombinations detected between MAOB and DXS1055 and between DXS1220 and DXS1001 place the disease locus between Xp11.3 and Xq23. Among the genes known to map to this region is the XNP gene for the alpha-thalassemia/mental retardation syndrome (ATR-X). This fact, along with the phenotypic similarity between our patients and ATR-X males, led us to consider XNP as a candidate gene for this family. X-inactivation studies provided further evidence for the involvement of XNP by showing completely skewed X-inactivation patterns in the three obligate carrier females, a pattern characteristic of carriers of XNP mutations.