TABLE 4

Common Recognizable XLID Syndromes

SyndromeCommon ManifestationsGene, Location
Aarskog syndromeShort stature, hypertelorism, downslanting palpebral fissures, joint hyperextensibility, shawl scrotumFGD1, Xp11.21
AdrenoleukodystrophyVariable and progressive vision and hearing loss, spasticity, neurological deterioration associated with demyelination of the central nervous system and adrenal insufficiencyABCD1, Xq28
Aicardi syndromeAgenesis of the corpus callosum, lacunar chorioretinopathy, costovertebral anomalies, seizures in females_____, Xp22
Allan–Herndon syndromeGeneralized muscle hypoplasia, childhood hypotonia, ataxia, athetosis, dysarthria, progressing to spastic paraplegiaMCT8 (SLC16A2), Xq13
ARX-related syndromes (includes Partington, Proud, West, XLAG syndromes and nonsyndromal XLMR)Partington: dysarthria, dystonia, hyperreflexia, seizures. West: infantile spasms, hypsarrhythmia. Proud: microcephaly, ACC, spasticity, seizures, ataxia, genital anomalies. XLAG: lissencephaly, seizures, genital anomaliesARX, Xp22.3
ATRX syndrome (includes ARTX, Chudley–Lowry, Carpenter–Waziri, Holmes–Gang, and Martinez spastic paraplegia syndromes and nonsyndromal XLMR)Short stature, microcephaly, hypotonic facies with hypertelorism, small nose, open mouth and prominent lips, brachydactyly, genital anomalies, hypotonia, in some cases hemoglobin H inclusions in erythrocytesXNP, (XH2) Xq13.3
Christianson syndromeShort stature, microcephaly, long narrow face, large ears, long straight nose, prominent mandible, general asthenia, narrow chest, long thin digits, adducted thumbs, contractures, seizures, autistic features, truncal ataxia, ophthalmoplegia, mutism, incontinence, hypoplasia of the cerebellum, and brain stemSLC9A6, Xq26
Coffin–Lowry syndromeShort stature, distinctive facies, large soft hands, hypotonia, joint hyperextensibility, skeletal changesRSK2, Xp22
Creatine transporter deficiencyNondysmorphic, autistic, possibly progressiveSLC6A8, Xq28
Duchenne muscular dystrophyPseudohypertrophic muscular dystrophyDMD, Xp21.3
Fragile X syndromeProminent forehead, long face, recessed midface, large ears, prominent mandible, macroorchidismFMR1, Xq27.3
Hunter syndromeProgressive coarsening of face, thick skin, cardiac valve disease, joint stiffening, dysostosis multiplexIDS, Xq28
Incontinentia pigmentiSequence of cutaneous blistering, verrucous thickening, and irregular pigmentation. May have associated CNS, ocular abnormalitiesNEMO (IKB6KG), Xq28
Lesch–Nyhan syndromeChoreoathetosis, spasticity, seizures, self-mutilation, uric acid urinary stonesHPRT, Xq26
Lowe syndromeShort stature, cataracts, hypotonia, renal tubular dysfunctionOCRL, Xq26.1
MECP2 duplication syndromeHypotonia, progressing to spastic paraplegia, recurrent infectionsMECP2, Xq28
Menkes syndromeGrowth deficiency, full cheeks, sparse kinky hair, metaphyseal changes, limited spontaneous movement, hypertonicity, seizures, hypothermia, lethargy, arterial tortuosity, death in early childhoodATP7A, Xpl3.3
Pelizaeus–Merzbacher diseaseNystagmus, truncal hypotonia, progressive spastic paraplegia, ataxia, dystoniaPLP, Xq21.1
Renpenning syndrome (includes Sutherland–Haan, cerebropalatocardiac, Golabi–Ito–Hall, Porteous syndromeShort stature, microcephaly, small testes. May have ocular or genital abnormalitiesPQBP1, Xp11.3
Rett syndromeXLMR in girls, cessation and regression of development in early childhood, truncal ataxia, autistic features, acquired microcephalyMECP2, Xq28
X-linked hydrocephaly-MASA spectrumHydrocephalus, adducted thumbs, spastic paraplegiaL1CAM, Xq28
  • Reproduced with permission from Stevenson and Schwartz.46