"LIS2" redirects here. For the video game, see Life Is Strange 2 . Not to be confused with Roberts syndrome . Norman–Roberts syndrome Other names Microlissencephaly type A, Lissencephaly 2 This condition is inherited in an autosomal recessive manner Specialty Neurology Norman–Roberts syndrome , is a rare form of microlissencephaly caused by a mutation in the RELN gene. [1] A small number of cases have been described. The syndrome was first reported by Margaret Grace Norman and M. Roberts et al. in 1976. [2] Lack of reelin prevents normal layering of the cerebral cortex and disrupts cognitive development. Patients have cerebellar hypoplasia and suffer from congenital lymphedema and hypotonia . The disorder is also associated with myopia , nystagmus and generalized seizures. [ citation needed ] Norman–Roberts syndrome is one of two known disorders caused by a disruption of the reelin -signaling pathway.

Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus , which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem). Individuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support.

Lissencephaly syndrome, Norman-Roberts type is characterised by the association of lissencephaly type I with craniofacial anomalies (severe microcephaly, a low sloping forehead, a broad and prominent nasal bridge and widely set eyes) and postnatal growth retardation. Epidemiology The prevalence is unknown. Clinical description Severe intellectual deficit, spasticity and epilepsy are also present. Etiology Mutations in the RELN gene (7q22) have been identified in some patients. Genetic counseling Transmission is autosomal recessive.

Lissencephaly 2 is an inherited condition characterized by classical lissencephaly in association with certain abnormalities of the skull and facial (craniofacial) region, such as a low, sloping forehead; abnormal prominence of the back portion of the head (occiput); a broad, prominent nasal bridge; and widely set eyes (ocular hypertelorism). Additional symptoms and findings typically include severe or profound intellectual disability, seizures, abnormally increased muscle tone ( hypertonia ), exaggerated reflexes (hyperreflexia), and severe growth failure. This condition is inherited in an autosomal recessive fashion. Mutations in the RELN gene have been identified in some affected individuals.

In addition, affected individuals have moderate to severe intellectual disability and distinctive physical features, including short stature; chubbiness; an unusually small head size (microcephaly ); a wide, short skull (brachycephaly ); a short, broad neck ; and facial features described as coarse . ... Problems with autonomic nerve cells (autonomic neurons), which control involuntary body functions such as heart rate, digestion, and breathing, result in several features of spastic paraplegia type 49.

Patients also have intellectual disability and dysmorphic features, including mild brachycephalic microcephaly, short broad neck, low anterior hairline and coarse face.

A rare, genetic, neurological disorder characterized by parkinsonian features (including resting or action tremor, cogwheel rigidity, hypomimia and bradykinesia) associated with variably penetrant spasticity, hyperactive deep tendon reflexes and Babinski sign.

A rare, syndromic intellectual disability characterized by hypotonia, developmetal delay, absent or severly delayed speech development, intellectual disability, obstructive sleep apnea, mild dysmorphic facial features and behavioral abnormalities. Epilepsy, ataxia and nystagmus have also been reported.

People with this syndrome usually present with developmental delay (especially delays in speech), low muscule tone (hypotonia), failure to thrive, mildly unusual facial features (broad forehead, widely-spaced eyes (hypertelorism), big and low-set ears, flat nasal bridge, and thin upper lip), and breathing difficulties when sleeping (sleep apnea). ... Other signs and symptoms may include autistic features, seizures, lack of coordination (ataxia), behavioral problems, crossed-eyes (strabismus), and an abnormal lateral curvature of the spine (scoliosis).

Contents 1 Signs and symptoms 2 Diagnosis 3 History 4 References Signs and symptoms [ edit ] Xia-Gibbs Syndrome is associated with symptoms including global developmental delay, hypotonia, obstructive sleep apnea, seizures, retrocerebellar cyst, delayed myelination, thinned corpus callosum, cutis aplasia, cortical visual impairment, micrognathia and mild dysmorphic features. Diagnosis [ edit ] Diagnosis requires diagnosis by whole-exome sequencing done by a genetic specialist. ... Gibbs et al . [6] Four patients were identified in the paper which recorded the initial discovery and their clinical features were reported, including global developmental delay, hypotonia, obstructive sleep apnea, intellectual disability and seizures. The publication of the paper and discovery of the new condition was reported in the media including in Science Daily and in Baylor College of Medicine News. [7] [8] [9] Subsequent research has identified and reported the clinical features of an additional seven patients and there are now known to be twenty confirmed cases. [10] References [ edit ] ^ "Ahdc1-Related Intellectual Disability-Obstructive Sleep Apnea-Mild Dysmorphism Syndrome disease: Malacards - Research Articles, Symptoms, Drugs, Genes, Clinical Trials" . www.malacards.org .

A number sign (#) is used with this entry because of evidence that Xia-Gibbs syndrome is caused by heterozygous mutation in the AHDC1 gene (615790) on chromosome 1p36. Clinical Features Xia et al. (2014) reported 4 unrelated children with mental retardation. All had failure to thrive, hypotonia, and delayed psychomotor development with absent or poor expressive language. Mild dysmorphic features were present, including low-set or protuberant ears, flat nasal bridge, esotropia, hypertelorism, up- or downslanting palpebral fissures, and micrognathia.

More variable manifestations are hearing loss, cortical visual impairment, abnormalities of fingers and/or toes, congenital cardiac anomalies, kyphoscoliosis, dysmorphic facial features, abnormal sleep pattern, and seizures, among others.

Description Cole-Carpenter syndrome is characterized by bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features (Cole and Carpenter, 1987). Genetic Heterogeneity of Cole-Carpenter Syndrome Cole-Carpenter syndrome-2 (CLCRP2; 616294) is caused by mutation in the SEC24D gene (607186). Clinical Features Cole and Carpenter (1987) described a seemingly new osteogenesis imperfecta-like disorder (see 166200) in 2 unrelated infants. Both had bone deformities and multiple fractures reminiscent of OI but also had ocular proptosis with orbital craniosynostosis, hydrocephalus, and distinctive facial features. Both infants were normal at birth; before the first birthday, however, recurrent diaphyseal fractures of the weight-bearing bones had occurred. ... In the first case the mother was noted to have somewhat shallow orbits and her father and grandmother had similar features; a paternal aunt had been examined for hyperthyroidism because of clinically evident proptosis. ... Amor et al. (2000) reported a girl with clinical features similar to the 2 cases presented by Cole and Carpenter (1987).

For a general phenotypic description and discussion of genetic heterogeneity of Cole-Carpenter syndrome, see CLCRP1 (112240). Clinical Features Garbes et al. (2015) reported a German boy with multiple pre- and postnatal fractures and craniofacial malformations. ... At 7 years of age he had moderately reduced bone mineral density, macrocephaly of postnatal onset, and short stature, with facial features reminiscent of Cole-Carpenter syndrome. ... She presented during the neonatal period with blue-gray sclerae, osteopenia, wormian bones, and deformities of the the long bones. No dysmorphic craniofacial features were present. Her coronal sutures were patent and her anterior fontanel was enlarged but not to the extent described in the patients reported by Garbes et al. (2015). ... Takeyari et al. (2018) reported a 15-year-old Japanese boy with features consistent with Cole-Carpenter syndrome-2. ... Garbes et al. (2015) noted overlap between features of these patients and individuals with craniolenticulosutural dysplasia (CLSD; 607812), which is caused by mutation in a related gene (SEC23A; 610511), but concluded that the phenotype of their patients more closely resembled that of Cole-Carpenter syndrome.

An extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia).

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, short stature, skeletal abnormalities (such as brachydactyly and vertebral anomalies), obesity, cardiac, respiratory, and genitourinary anomalies, and dysmorphic facial features (including coarse facies, thick eyebrows, synophrys, hypertelorism, short, upturned nose, and long philtrum).

"CHOPS" is an acronym for the primary signs and symptoms associated with the condition, including cognitive impairment, coarse facial features, heart defects , obesity, pulmonary (lung) problems, short stature, and skeletal abnormalities.

The name "CHOPS" is an abbreviation for a list of features of the disorder including cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities. Children with CHOPS syndrome have intellectual disability and delayed development of skills such as sitting and walking. Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth. ... They also have skeletal differences including unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae). Other features that can occur in CHOPS syndrome include a small head size (microcephaly ); hearing loss; clouding of the lens of the eye (cataract); a single, horseshoe-shaped kidney; and, in affected males, undescended testes (cryptorchidism).

It is likely this syndrome is underdiagnosed, since many of the features are nonspecific [Sirmaci et al 2011]. ... The craniofacial findings may not always be apparent, so lack of these features does not preclude the diagnosis. ... Prevalence KBG syndrome was initially thought to be quite rare; however, it is likely underdiagnosed due to mild and nonspecific features in some affected individuals especially before eruption of the permanent dentition [Sirmaci et al 2011]. ... Disorders to Consider in the Differential Diagnosis of KBG Syndrome View in own window DiffDx Disorder Gene(s) MOI Clinical Features of the DiffDx Disorder Overlapping w/KBG syndrome Distinguishing from KBG syndrome Cornelia de Lange syndrome NIPBL SMC1A HDAC8 SMC3 RAD21 AD XL Facial features DD Growth restriction Hearing loss Cryptorchidism Typically: Head circumference small ID more severe Silver-Russell syndrome See footnote 1. ... Pregnancy management should be tailored to the specific features present in the affected woman.

Sirmaci et al. (2011) noted that it is likely that KBG syndrome is underdiagnosed, since many of the features, including intellectual disability, are mild, and none of the features is a prerequisite for diagnosis. Clinical Features Herrmann et al. (1975) described 2 families in which multiple members had short stature, characteristic facies (telecanthus, wide eyebrows, brachycephaly), macrodontia, mental retardation, and skeletal anomalies (abnormal vertebrae, short metacarpals, short femoral necks). ... All 3 patients had developmental delay and mild to moderate mental retardation. Physical features included short stature (less than 3rd percentile), a triangular face, low anterior and posterior hairlines, bushy eyebrows, large prominent ears, a long philtrum, anteverted nostrils with hypoplastic alae nasi, and wide upper central incisors. ... The patients were ascertained from a larger cohort of patients with features consistent with Cornelia de Lange syndrome (see, e.g., CDLS1, 122470), thus showing phenotypic overlap between the 2 disorders. All had normal head circumference; detailed clinical features were not provided. INHERITANCE - Autosomal dominant GROWTH Height - Short stature (less than tenth percentile) HEAD & NECK Head - Microcephaly Face - Round face early in life - Triangular face later in life - Long philtrum Ears - Large prominent ears Eyes - Hypertelorism - Telecanthus - Long palpebral fissures - Broad bushy eyebrows Nose - Anteverted nares - Hypoplastic alae nasi Teeth - Macrodontia - Wide upper central incisors - Ridged teeth - Fused incisors - Oligodontia CHEST Ribs Sternum Clavicles & Scapulae - Cervical rib fusion - Accessory cervical ribs GENITOURINARY Internal Genitalia (Male) - Cryptorchidism SKELETAL - Delayed bone maturation Spine - Vertebral body fusion - Vertebral arch abnormalities - Thoracic kyphosis Hands - Clinodactyly - Decreased hand length - Syndactyly SKIN, NAILS, & HAIR Skin - Simian crease Hair - Broad bushy eyebrows - Low anterior hairline - Low posterior hairline NEUROLOGIC Central Nervous System - Developmental delay - Mental retardation - EEG anomalies (in some patients) - Seizures (in some patients) MISCELLANEOUS - Male to female ratio 21:8 MOLECULAR BASIS - Caused by mutation in the ankyrin repeat domain-containing protein 11 gene (ANKRD11, 611192.0001 ) ▲ Close

Behavioral disturbances including hyperactivity, aggressiveness, attention deficit and autism spectrum disorders are recognized as constant clinical features. Developmental delay includes delayed motor milestones and markedly delayed speech and is almost always present in all patients. Characteristic facial dysmorphism is prominent in about half of the patients, consisting of triangular face, wide eyebrows with mild synophrys, hypertelorism, prominent ears and nasal bridge with bulbous nasal tip, long flat philtrum and thin upper lip. The hallmark feature, macrodontia, is observed in about 80% of cases; additional dental findings include oligo- or hypodontia, premature teeth loss in adults and enamel hypoplasia. ... Seizures, feeding difficulties, recurrent otitis media/hearing loss, palatal abnormalities and precocious puberty are notable additional features associated with KBGS. Etiology KBGS is caused by loss-of function alterations (pathogenic variants and copy number variations) affecting the ANKRD11 gene (16q24.3) which encodes ankyrin repeat domain-containing protein 11.

KBG syndrome Symptoms macrodontia , brachycephaly , hypertelorism , synophrys , long philtrum , thin upper lip KBG syndrome is a genetic disease that is the result of a mutation in the ANKRD11 gene. [1] Features include unusually large upper front teeth ( macrodontia ), wide, short skull ( brachycephaly ), widely spaced eyes ( hypertelorism ), and wide eyebrows that may grow together in the middle ( synophrys ). [2] The syndrome was first described by Herrmann in 1975 in three distinct families. [3] Herrmann proposed the name KBG syndrome after the initials of affected families last names. [4] References [ edit ] ^ Online Mendelian Inheritance in Man (OMIM): KBG syndrome - 148050 ^ "KBG syndrome" .

KBG syndrome is a rare condition characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. Specific signs and symptoms may include delayed bone age; abnormalities of the bones of the spine, ribs, and/or hands; large teeth (macrodontia); short stature; developmental delay; and behavioral or emotional issues. Less common features may include hearing loss, seizures, and congenital heart defects.

Bone dysplasia lethal Holmgren type (BDLH) is a lethal bone dysplasia characterized at birth by low birth weight, a rhizomelic dwarfism, bent femora and short chest producing asphyxia. It was described in three siblings from healthy, non-consanguineous parents of Finnish and in four siblings from non-consanguineous parents of French origin with no family history of dwarfism. The initial cases could have been diagnosed as Desbuquois syndrome, or a recessive Larsen syndrome. There has been no further description of BDLH in the literature since 1988.

A number sign (#) is used with this entry because of evidence that geroderma osteodysplasticum (GO) is caused by homozygous or compound heterozygous mutation in the GORAB gene (607983) on chromosome 1q24. Clinical Features As the name indicates, the features of this disorder include changes in the skin suggesting precocious aging and osseous changes including osteoporosis and multiple lines like growth rings of trees. ... Eight individuals from 3 families were diagnosed with GO. Distinctive features of GO included skin wrinkling limited to the dorsum of the hands, feet, and abdomen, normal-sized fontanels, normal teeth, bowed long bones, and osteopenia with frequent fractures. ... In 1 of the Omani families originally reported by Rajab et al. (2008) with clinical features consistent with GO, Reversade et al. (2009) identified homozygosity for a missense mutation in the PYCR1 gene (179035.0008; see ARCL2B, 612940).

Geroderma osteodysplastica is a rare disease characterized by lax, wrinkled skin, loose joints and a typical face with a prematurely aged appearance. Bone problems may include severe osteoporosis leading to frequent fractures, underdeveloped cheekbones and jaw (malar and mandibular hypoplasia) and a variable degree of growth deficiency. This condition is caused by mutations in the GORAB gene. Inheritance is autosomal recessive.

Specialty Medical genetics Gerodermia osteodysplastica ( GO ), is a rare autosomal recessive [2] connective tissue disorder included in the spectrum of cutis laxa syndromes . [2] [3] Usage of the name "Walt Disney dwarfism" is attributed to the first known case of the disorder, documented in a 1950 journal report, in which the authors described five affected members from a Swiss family as having the physical appearance of dwarves from a Walt Disney film. [4] [5] The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end. [1] [6] Contents 1 Presentation 2 Genetics 3 Diagnosis 3.1 Differential diagnosis 4 Treatment 5 See also 6 References 7 External links Presentation [ edit ] Gerodermia osteodysplastica is characterized by symptoms and features which affect the connective tissues , skin and skeletal system . [ citation needed ] These are: wrinkly, loose skin over the face , abdomen , and extremities ( hands , feet) on the dorsal sides usually worsened by chronic joint laxity and hyperextensibility ; [7] [8] fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers ; [9] osteopenia and osteoporosis , with associated fractures ; [6] [7] malar hypoplasia (underdeveloped cheek bone), [10] maxillary hypoplasia (underdeveloped upper jaw ), [6] mandibular prognathism (protrusion of the lower jaw and chin ), [10] [11] bowed long bones , [6] platyspondyly (flattened spine ) related to vertebral collapse; [6] [12] kyphoscoliosis ( scoliosis with kyphosis , or "hunch back"), [12] metaphyseal peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal region of the bone, near the knee ); [13] and the overall physical effects and facial appearance of dwarfism with premature aging. [5] [14] Other features and findings include: intrauterine growth retardation, [8] congenital hip dislocations , [8] winged scapulae ( shoulder blades ), [12] pes planus (fallen arches ), [12] pseudoepiphyses of the second metacarpals (upper bone of the fingers ), [12] hypotelorism (close-set eyes ), [7] malformed ears , [14] developmental delay , [8] failure to thrive [7] and abnormal electroencephalograph (EEG) readings. [14] Dental and orthodontal abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. ... The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. [ citation needed ] It has been associated with SCYL1BP1 . [16] Diagnosis [ edit ] Differential diagnosis [ edit ] Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa, wrinkly skin syndrome (WSS, Online Mendelian Inheritance in Man (OMIM): 278250 ), are similar to such an extent that both disorders were believed to be variable phenotypes of a single disorder. [7] [8] Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum. [6] [8] While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. [6] Also, as the fontanelles ("soft spots") are usually normal on the heads of infants with GO, they are often enlarged in WSS infants. [6] While WSS is associated with mutations of genes on chromosomes 2 , 5 , 7 , 11 and 14 ; GO has been linked to mutations in the protein GORAB. [17] A serum sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients. [6] But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. [13] Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development. [13] Treatment [ edit ] This section is empty.

Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with adrenocorticotrophin hormone (ACTH) independent Cushing syndrome (see this term) and is characterized by small to normal sized adrenal glands containing multiple small cortical pigmented nodules (less than 1 cm in diameter). Epidemiology The prevalence of endogenous Cushing syndrome (CS; see this term) is estimated at 1/26,000. PPNAD is responsible for less than 2% of cases. PPNAD is more frequent in females, especially after puberty. Clinical description Although the majority of cases are diagnosed in the 2nd and 3rd decades of life, a substantial proportion of patients present during early childhood (2-3 years). Patients with PPNAD often present with atypical CS, which is characterized by an asthenic, rather than obese, body habitus caused by severe osteoporosis, short stature and severe muscle and skin wasting.

This article is an orphan , as no other articles link to it . Please introduce links to this page from related articles ; try the Find link tool for suggestions. ( September 2012 ) Qazi–Markouizos syndrome Other names Dysharmonic skeletal maturation-muscular fiber disproportion syndrome [1] Qazi–Markouizos syndrome is a rare hereditary condition characterized by non-progressive, congenital hypotonia , severe intellectual disability, an increased proportion of type 2 muscle fibers , which additionally exhibited increased size, as well as dysharmonic skeletal maturation . [2] [3] To date, the molecular mechanism of Qazi–Markouizos syndrome, which is also known as Puerto Rican infant hypotonia syndrome, [4] remains unknown. References [ edit ] ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Qazi Markouizos syndrome" . www.orpha.net . Retrieved 16 March 2019 . ^ Qazi, QH; Markouizos, D; Rao, C; Sheikh, T; Beller, E; Kula, R (May 1994). "A syndrome of hypotonia, psychomotor retardation, seizures, delayed and dysharmonic skeletal maturation, and congenital fibre type disproportion" . Journal of Medical Genetics . 31 (5): 405–9. doi : 10.1136/jmg.31.5.405 .

A rare, genetic, syndromic intellectual disability disorder characterized by non-progressive, congenital, marked, central hypotonia, severe psychomotor delay and intellectual disability, chronic constipation, distended abdomen, abnormal dermatoglyphics, delayed and dysharmonic skeletal maturation, and preponderance of type 2 larger-sized muscle fibers. Additional features include narrow and high-arched palate, prominent nasal root, long philtrum, and open mouth with drooling, as well as variably present cryptorchidism, hypertelorism, and tapered fingers.

X-linked recessive disorder characterised by developmental delay Say–Meyer syndrome Other names Trigonocephaly-short stature-developmental delay syndrome Say–Meyer syndrome is inherited in an X-linked recessive manner. Say–Meyer syndrome is a rare X-linked genetic disorder that is mostly characterized as developmental delay . It is one of the rare causes of short stature . It is closely related with trigonocephaly (a misshapen forehead due to premature fusion of bones in the skull). People with Say–Meyer syndrome have impaired growth, deficits in motor skills development and mental state. [1] [2] It is suggested that it is from a X-linked transmission. [3] Contents 1 Signs and symptoms 1.1 Growth and development 2 Causes 3 Diagnosis 4 Treatment 4.1 Surgical 5 History 6 References 7 External links Signs and symptoms [ edit ] Common signs of Say–Meyer syndrome are trigonocephaly as well as head and neck symptoms. The head and neck symptoms come in the form of craniosynostosis affecting the metopic suture (the dense connective tissue structure that divides the two halves of the skull in children which usually fuse together by the age of six).

A rare developmental defect during embryogenesis characterized by premature closure of metopic sutures and/or other sutures, short stature, and developmental delay. Dysmorphic features include trigonocephaly, metopic ridge, narrow forehead, bitemporal narrowing, arched eyebrows, hypotelorism, deep-set eyes, epicanthal folds, strabismus, wide nasal bridge, small pointed nose, anteverted nostrils, long philtrum, low-set ears, malar flattening, narrow mouth, thin lips, high-arched palate, crowded teeth, and micrognathia.

The diagnosis of SIOD is established in a proband with the characteristic clinical and radiographic features. Identification of biallelic pathogenic variants in SMARCAL1 on molecular genetic testing establishes the diagnosis if clinical features are inconclusive. ... The renal pathology has been reported as focal segmental glomerulosclerosis without pathognomonic features in 83% of individuals. T-cell deficiency (76% of tested individuals). ... The T cells are predominantly of a memory (CD45R0+CD45RA-) surface phenotype. Characteristic facial features that include a wide, depressed nasal bridge (65%) and a broad nasal tip (78%) Hyperpigmented macules (70%) on the trunk and occasionally extending onto the arms, neck, and legs Establishing the Diagnosis The diagnosis of SIOD is established in a proband with the above clinical features. ... Total individuals with SIOD for whom the feature of interest has been reported to be present or absent 2. ... Physical features. Most affected individuals have hyperpigmented macules on the trunk and occasionally on the extremities, neck, and face.

A number sign (#) is used with this entry because of evidence that Schimke immunoosseous dysplasia (SIOD) is caused by homozygous or compound heterozygous mutation in the SMARCAL1 gene (606622) on chromosome 2q25. Clinical Features Schimke immunoosseous dysplasia was first described by Schimke et al. (1974) as 'chondroitin-6-sulfate mucopolysaccharidosis.' ... Studies suggested that malabsorption, demonstrated as increased serum immunoglobulin A anti-gliadan antibody, steatorrhea, and partial villous atrophy of the jejunum, is a previously unrecognized feature of Schimke immunoosseous dysplasia. ... He also had increased urinary excretion of chondroitin-6-sulfate, which was present in the patient reported by Schimke et al. (1974) but had rarely been described in later cases. He had radiographic features consistent with the diagnosis, and immunologic studies showed recurrent lymphopenia with persistent reduction of T lymphocytes. ... They concluded that, overall, the clinical features in the 2 groups were similar. Sigurdardottir et al. (2000) reported a 17-year-old patient with Schimke immunoosseous dysplasia, which they referred to as SID, who presented with mental retardation, partial complex seizures, and severely disruptive behaviors. ... The author suggested that future reports of immunoosseous dysplasia carefully document dental and oral findings to determine whether the condition includes dental abnormalities as one of its features. Boerkoel et al. (2000) identified reports of 25 patients with this disorder.

Schimke immunoosseous dysplasia (SIOD) is a condition that results in short stature, kidney disease (nephropathy), and a weakened immune system. Some people develop a severe form in early childhood, and others develop a milder form in childhood or later. Short stature is due to spondyloepiphyseal dysplasia , which involves abnormal development of the spine and the ends of the long bones. Nearly all people with SIOD have kidney disease, which progresses to end-stage renal disease . Most people with SIOD also have T-cell deficiency causing an increased risk for infections, which can be life-threatening.

A shortage of T cells causes a person to be more susceptible to illness. Other features frequently seen in people with this condition include an exaggerated curvature of the lower back (lordosis ); darkened patches of skin (hyperpigmentation), typically on the chest and back; and a broad nasal bridge with a rounded tip of the nose.